H M Holden

Summary

Affiliation: University of Wisconsin
Country: USA

Publications

  1. ncbi request reprint Galactokinase: structure, function and role in type II galactosemia
    H M Holden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Cell Mol Life Sci 61:2471-84. 2004
  2. ncbi request reprint Structure and function of enzymes of the Leloir pathway for galactose metabolism
    Hazel M Holden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 278:43885-8. 2003
  3. doi request reprint Biosynthetic enzymes of unusual microbial sugars
    Hazel M Holden
    Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA
    Curr Opin Struct Biol 20:543-50. 2010
  4. ncbi request reprint The crotonase superfamily: divergently related enzymes that catalyze different reactions involving acyl coenzyme a thioesters
    H M Holden
    Departments of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
    Acc Chem Res 34:145-57. 2001
  5. ncbi request reprint The structure of carbamoyl phosphate synthetase determined to 2.1 A resolution
    J B Thoden
    Institute for Enzyme Research, The Graduate School, and Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin Madison, 1710 University Avenue, Madison, Wisconsin 53705, USA
    Acta Crystallogr D Biol Crystallogr 55:8-24. 1999
  6. ncbi request reprint New reactions in the crotonase superfamily: structure of methylmalonyl CoA decarboxylase from Escherichia coli
    M M Benning
    Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
    Biochemistry 39:4630-9. 2000
  7. ncbi request reprint Iron-sulfur cluster cysteine-to-serine mutants of Anabaena -2Fe-2S- ferredoxin exhibit unexpected redox properties and are competent in electron transfer to ferredoxin:NADP+ reductase
    J K Hurley
    Department of Biochemistry, University of Arizona, Tucson, Arizona 85721, USA
    Biochemistry 36:15109-17. 1997
  8. ncbi request reprint Carbamoyl phosphate synthetase: closure of the B-domain as a result of nucleotide binding
    J B Thoden
    Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin Madison 53705, USA
    Biochemistry 38:2347-57. 1999
  9. ncbi request reprint The small subunit of carbamoyl phosphate synthetase: snapshots along the reaction pathway
    J B Thoden
    Department of Biochemistry, University of Wisconsin Madison 53705, USA
    Biochemistry 38:16158-66. 1999
  10. ncbi request reprint The binding of inosine monophosphate to Escherichia coli carbamoyl phosphate synthetase
    J B Thoden
    Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison, Madison, Wisconsin 53705, USA
    J Biol Chem 274:22502-7. 1999

Research Grants

  1. Structure-Function Analysis of Enzymes
    Hazel Holden; Fiscal Year: 2004
  2. X-ray Studies of Sugar-Modifying Enzymes
    Hazel Holden; Fiscal Year: 2005
  3. X-ray Studies of Sugar-Modifying Enzymes
    Hazel Holden; Fiscal Year: 2010
  4. STRUCTURAL STUDIES OF NUCLEOTIDE DEPENDENT ENZYMES
    Hazel Holden; Fiscal Year: 2001
  5. STRUCTURE/FUNCTION ANALYSIS OF ENZYMES
    Hazel Holden; Fiscal Year: 2000
  6. X-ray Studies of Sugar-Modifying Enzymes
    Hazel Holden; Fiscal Year: 2010

Collaborators

Detail Information

Publications91

  1. ncbi request reprint Galactokinase: structure, function and role in type II galactosemia
    H M Holden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Cell Mol Life Sci 61:2471-84. 2004
    ....
  2. ncbi request reprint Structure and function of enzymes of the Leloir pathway for galactose metabolism
    Hazel M Holden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 278:43885-8. 2003
  3. doi request reprint Biosynthetic enzymes of unusual microbial sugars
    Hazel M Holden
    Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA
    Curr Opin Struct Biol 20:543-50. 2010
    ..In this review we focus on the recent structural investigations of the bacterial N-acetyltransferases and the PLP-dependent aminotransferases that function on nucleotide-linked sugar substrates...
  4. ncbi request reprint The crotonase superfamily: divergently related enzymes that catalyze different reactions involving acyl coenzyme a thioesters
    H M Holden
    Departments of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
    Acc Chem Res 34:145-57. 2001
    ..This apparently is accomplished by two structurally conserved peptidic NH groups that provide hydrogen bonds to the carbonyl moieties of the acyl-CoA substrates and form an "oxyanion hole"...
  5. ncbi request reprint The structure of carbamoyl phosphate synthetase determined to 2.1 A resolution
    J B Thoden
    Institute for Enzyme Research, The Graduate School, and Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin Madison, 1710 University Avenue, Madison, Wisconsin 53705, USA
    Acta Crystallogr D Biol Crystallogr 55:8-24. 1999
    ..The carboxyphosphate and carbamoyl phosphate synthetic components, while topologically equivalent, are structurally different, as would be expected in light of their separate biochemical functions...
  6. ncbi request reprint New reactions in the crotonase superfamily: structure of methylmalonyl CoA decarboxylase from Escherichia coli
    M M Benning
    Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
    Biochemistry 39:4630-9. 2000
    ..The new constellation of putative functional groups observed in the active site of MMCD underscores the diversity of function in this superfamily...
  7. ncbi request reprint Iron-sulfur cluster cysteine-to-serine mutants of Anabaena -2Fe-2S- ferredoxin exhibit unexpected redox properties and are competent in electron transfer to ferredoxin:NADP+ reductase
    J K Hurley
    Department of Biochemistry, University of Arizona, Tucson, Arizona 85721, USA
    Biochemistry 36:15109-17. 1997
    ....
  8. ncbi request reprint Carbamoyl phosphate synthetase: closure of the B-domain as a result of nucleotide binding
    J B Thoden
    Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin Madison 53705, USA
    Biochemistry 38:2347-57. 1999
    ..Details concerning the geometries of the two active sites contained within the large subunit of CPS are described...
  9. ncbi request reprint The small subunit of carbamoyl phosphate synthetase: snapshots along the reaction pathway
    J B Thoden
    Department of Biochemistry, University of Wisconsin Madison 53705, USA
    Biochemistry 38:16158-66. 1999
    ..The results described here serve as a paradigm for other members of the Triad class of amidotranferases...
  10. ncbi request reprint The binding of inosine monophosphate to Escherichia coli carbamoyl phosphate synthetase
    J B Thoden
    Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison, Madison, Wisconsin 53705, USA
    J Biol Chem 274:22502-7. 1999
    ..This structural analysis reveals, for the first time, the detailed manner in which CPS accommodates nucleotide monophosphate effector molecules within the allosteric domain...
  11. ncbi request reprint High resolution X-ray structures of different metal-substituted forms of phosphotriesterase from Pseudomonas diminuta
    M M Benning
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 40:2712-22. 2001
    ..By measuring the anomalous X-ray data from crystals of the Zn(2+)/Cd(2+)-species, it has been possible to determine that the alpha-metal ion is zinc and the beta-site is occupied by cadmium...
  12. ncbi request reprint Crystallographic evidence for Tyr 157 functioning as the active site base in human UDP-galactose 4-epimerase
    J B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53705, USA
    Biochemistry 39:5691-701. 2000
    ..A low barrier hydrogen bond between the 4'-hydroxyl group of the sugar and O(gamma) of Ser 132 facilitates proton transfer from the sugar 4'-hydroxyl group to O(eta) of Tyr 157...
  13. ncbi request reprint Three-dimensional structure of ATP:corrinoid adenosyltransferase from Salmonella typhimurium in its free state, complexed with MgATP, or complexed with hydroxycobalamin and MgATP
    C B Bauer
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 40:361-74. 2001
    ..1 A from C5' of the ribose and is beyond the range of nucleophilic attack. This suggests that a conformational change occurs in the ternary complex when Co(III) is reduced to Co(I)...
  14. ncbi request reprint Molecular structure of Escherichia coli PurT-encoded glycinamide ribonucleotide transformylase
    J B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53705, USA
    Biochemistry 39:8791-802. 2000
    ..Strikingly, the amino group of GAR that is formylated during the reaction lies at 2.8 A from one of the gamma-phosphoryl oxygens of the AMPPNP...
  15. ncbi request reprint Dramatic differences in the binding of UDP-galactose and UDP-glucose to UDP-galactose 4-epimerase from Escherichia coli
    J B Thoden
    Department of Biochemistry, University of Wisconsin Madison 53705, USA
    Biochemistry 37:11469-77. 1998
    ....
  16. ncbi request reprint Human UDP-galactose 4-epimerase. Accommodation of UDP-N-acetylglucosamine within the active site
    J B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53705, USA
    J Biol Chem 276:15131-6. 2001
    ..This combination of a larger active site cavity and amino acid residue replacement most likely accounts for the inability of the E. coli enzyme to interconvert UDP-GlcNAc and UDP-GalNAc...
  17. ncbi request reprint Three-dimensional structure of Escherichia coli asparagine synthetase B: a short journey from substrate to product
    T M Larsen
    Department of Biochemistry, University of Wisconsin, Madison 53706, USA
    Biochemistry 38:16146-57. 1999
    ....
  18. ncbi request reprint Three-dimensional structure of N5-carboxyaminoimidazole ribonucleotide synthetase: a member of the ATP grasp protein superfamily
    J B Thoden
    Department of Biochemistry, University of Wisconsin Madison 53705, USA
    Biochemistry 38:15480-92. 1999
    ..The P loop is proposed to bind the phosphate of AIR on the basis of similar binding sites observed in PurN and PurE and proposed in PurD and PurT, four other enzymes in the purine pathway...
  19. ncbi request reprint Crystal structures of the oxidized and reduced forms of UDP-galactose 4-epimerase isolated from Escherichia coli
    J B Thoden
    Institute for Enzyme Research, University of Wisconsin, Madison, Wisconsin 53705 USA
    Biochemistry 35:2557-66. 1996
    ..Thus it may be speculated that an amino acid residue, other than glutamate, aspartate, or histidine, may be functioning as the active site base...
  20. ncbi request reprint Molecular structure of the NADH/UDP-glucose abortive complex of UDP-galactose 4-epimerase from Escherichia coli: implications for the catalytic mechanism
    J B Thoden
    Institute for Enzyme Research, Graduate School, University of Wisconsin, Madison 53705, USA
    Biochemistry 35:5137-44. 1996
    ..Furthermore, the abortive complex model described here suggests that Ser 124 and Tyr 149 are likely to play important roles in the catalytic mechanism of the enzyme...
  21. ncbi request reprint Structural analysis of the H166G site-directed mutant of galactose-1-phosphate uridylyltransferase complexed with either UDP-glucose or UDP-galactose: detailed description of the nucleotide sugar binding site
    J B Thoden
    Department of Biochemistry, University of Wisconsin Madison, 53705, USA
    Biochemistry 36:1212-22. 1997
    ..As such, the mutant protein structures presented here represent valid models for understanding substrate recognition and binding in the native galactose-1-phosphate uridylyltransferase...
  22. ncbi request reprint Molecular structures of the S124A, S124T, and S124V site-directed mutants of UDP-galactose 4-epimerase from Escherichia coli
    J B Thoden
    Institute for Enzyme Research, Graduate School, University of Wisconsin, Madison 53705, USA
    Biochemistry 36:10685-95. 1997
    ..NADH. UDP complex...
  23. ncbi request reprint Molecular basis for severe epimerase deficiency galactosemia. X-ray structure of the human V94m-substituted UDP-galactose 4-epimerase
    J B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin, 53706, USA
    J Biol Chem 276:20617-23. 2001
    ..The net effect of the V94M substitution is an opening up of the Ala(93) to Glu(96) surface loop, which allows free rotation of the sugars into nonproductive binding modes...
  24. ncbi request reprint Movement of the biotin carboxylase B-domain as a result of ATP binding
    J B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53705, USA
    J Biol Chem 275:16183-90. 2000
    ..A comparison of this closed form of biotin carboxylase with carbamoyl-phosphate synthetase is presented...
  25. ncbi request reprint Molecular structure of galactokinase
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 278:33305-11. 2003
    ..Most likely these residues play key roles in catalysis. The structure of galactokinase described here serves as a model for understanding the functional consequences of point mutations known to result in Type II galactosemia in humans...
  26. pmc High-resolution X-ray structure of UDP-galactose 4-epimerase complexed with UDP-phenol
    J B Thoden
    Institute for Enzyme Research, Graduate School, University of Wisconsin, Madison 53705, USA
    Protein Sci 5:2149-61. 1996
    ....
  27. ncbi request reprint Molecular structure of dihydroorotase: a paradigm for catalysis through the use of a binuclear metal center
    J B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 40:6989-97. 2001
    ..The ensuing tetrahedral intermediate collapses with C-O bond cleavage and expulsion of the hydroxide which then bridges the binuclear metal center...
  28. ncbi request reprint Structure of carbamoyl phosphate synthetase: a journey of 96 A from substrate to product
    J B Thoden
    Institute for Enzyme Research, College of Agriculture, University of Wisconsin, Madison 53705, USA
    Biochemistry 36:6305-16. 1997
    ..The reactive and unstable enzyme intermediates must therefore be sequentially channeled from one active site to the next through the interior of the protein...
  29. ncbi request reprint Three-dimensional structure of myosin subfragment-1: a molecular motor
    I Rayment
    Department of Biochemistry, University of Wisconsin, Madison 53705
    Science 261:50-8. 1993
    ..This structure of a molecular motor was determined by single crystal x-ray diffraction. The data provide a structural framework for understanding the molecular basis of motility...
  30. ncbi request reprint Carbamoyl phosphate synthetase: an amazing biochemical odyssey from substrate to product
    H M Holden
    Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin Madison, 53705, USA
    Cell Mol Life Sci 56:507-22. 1999
    ..In this review, we highlight the recent biochemical and X-ray crystallographic results that have led to a more complete understanding of this finely tuned instrument of catalysis...
  31. ncbi request reprint Structure-function relationships in Anabaena ferredoxin: correlations between X-ray crystal structures, reduction potentials, and rate constants of electron transfer to ferredoxin:NADP+ reductase for site-specific ferredoxin mutants
    J K Hurley
    Department of Biochemistry, University of Arizona, Tucson, Arizona 85721, USA
    Biochemistry 36:11100-17. 1997
    ..Rather, the kinetic properties are most likely controlled by the specific orientations of the proteins within the transient electron-transfer complex...
  32. ncbi request reprint Molecular structure of human galactose mutarotase
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 279:23431-7. 2004
    ..In the C. elegans protein, the first 17 residues are missing, thereby reducing the total number of beta-strands by one...
  33. pmc Structure of the beta 2 homodimer of bacterial luciferase from Vibrio harveyi: X-ray analysis of a kinetic protein folding trap
    J B Thoden
    Institute for Enzyme Research, University of Wisconsin, Madison 53705, USA
    Protein Sci 6:13-23. 1997
    ..In fact, the subunit:subunit interfaces observed in both the beta 2 homodimer and alpha beta heterodimer are remarkably similar in hydrogen-bonding patterns and buried surface areas...
  34. ncbi request reprint The molecular architecture of human N-acetylgalactosamine kinase
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 280:32784-91. 2005
    ..From this investigation, the geometry of the GalNAc kinase active site before and after catalysis has been revealed, and the determinants of substrate specificity have been defined on a molecular level...
  35. ncbi request reprint The molecular architecture of galactose mutarotase/UDP-galactose 4-epimerase from Saccharomyces cerevisiae
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA
    J Biol Chem 280:21900-7. 2005
    ..The two active sites of Gal10p are separated by over 50 A. This investigation represents the first structural analysis of a dual function enzyme in the Leloir pathway...
  36. doi request reprint Accommodation of GDP-linked sugars in the active site of GDP-perosamine synthase
    Paul D Cook
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 47:10685-93. 2008
    ....
  37. ncbi request reprint The structure of 4-hydroxybenzoyl-CoA thioesterase from arthrobacter sp. strain SU
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706 1544, USA
    J Biol Chem 278:43709-16. 2003
    ..Although these two bacterial thioesterases demonstrate equivalent catalytic efficiencies, substrate specificities, and metabolic functions, their quaternary structures, CoA-binding sites, and catalytic platforms are decidedly different...
  38. ncbi request reprint Structural investigation of the antibiotic and ATP-binding sites in kanamycin nucleotidyltransferase
    L C Pedersen
    Institute for Enzyme Research, Graduate School, University of Wisconsin, Madison 53705, USA
    Biochemistry 34:13305-11. 1995
    ..The 4'-hydroxyl group of the antibiotic is approximately 5 A from the alpha-phosphorus of the nucleotide and is in the proper orientation for a single in-line displacement attack at the phosphorus.(ABSTRACT TRUNCATED AT 250 WORDS)..
  39. ncbi request reprint Molecular structure of human galactokinase: implications for type II galactosemia
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 280:9662-70. 2005
    ....
  40. pmc Two site-directed mutations are required for the conversion of a sugar dehydratase into an aminotransferase
    Paul D Cook
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 48:5246-53. 2009
    ..Here we present a combined structural and functional analysis of the ColD S187N/H188K mutant protein that, indeed, has been converted from a sugar dehydratase into an aminotransferase...
  41. doi request reprint GDP-perosamine synthase: structural analysis and production of a novel trideoxysugar
    Paul D Cook
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 47:2833-40. 2008
    ..Details describing the X-ray structural investigation of GDP-perosamine synthase and the enzymatic synthesis of GDP-4-amino-3,4,6-trideoxy- d-mannose are presented...
  42. pmc Structural interpretation of the mutations in the beta-cardiac myosin that have been implicated in familial hypertrophic cardiomyopathy
    I Rayment
    Institute for Enzyme Research, Graduate School, University of Wisconsin, Madison 53705 4098, USA
    Proc Natl Acad Sci U S A 92:3864-8. 1995
    ..The remaining five mutations are in the myosin rod. The locations of these mutations provide insight into the way they impair the functioning of this molecular motor and also into the mechanism of energy transduction...
  43. ncbi request reprint Carbamoyl phosphate synthetase: a tunnel runs through it
    H M Holden
    Department of Biochemistry University of Wisconsin Madison WI 53706 USA
    Curr Opin Struct Biol 8:679-85. 1998
    ..The recently determined three-dimensional structure of carbamoyl phosphate synthetase sets a new long distance record in that the three active sites are separated by nearly 100 A...
  44. ncbi request reprint Structural and kinetic studies of sugar binding to galactose mutarotase from Lactococcus lactis
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706 1544, USA
    J Biol Chem 277:45458-65. 2002
    ..These different binding modes correlate with both the observed kinetic parameters and the presence or absence of a hydrogen bond between the guanidinium group of Arg-71 and the C-4 hydroxyl group of the sugar ligand...
  45. ncbi request reprint Evolution of enzymatic activity in the enolase superfamily: functional studies of the promiscuous o-succinylbenzoate synthase from Amycolatopsis
    Erika A Taylor Ringia
    Departments of Biochemistry and Chemistry, University of Illinois, Urbana, IL 61801, USA
    Biochemistry 43:224-9. 2004
    ....
  46. ncbi request reprint Functional significance of Glu-77 and Tyr-137 within the active site of isoaspartyl dipeptidase
    Ricardo Marti-Arbona
    Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA
    Bioorg Chem 33:448-58. 2005
    ..The positioning of the side-chain carboxylate of Glu-77 is consistent with the formation of an ion pair interaction with the free alpha-amino group of the substrate...
  47. ncbi request reprint High resolution X-ray structure of galactose mutarotase from Lactococcus lactis
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 277:20854-61. 2002
    ..Strikingly, the carboxylate group of Glu(304) is situated at approximately 2.7 A from the 1'-hydroxyl group of galactose, thereby suggesting its possible role as a general acid/base group...
  48. pmc Molecular architecture of DesI: a key enzyme in the biosynthesis of desosamine
    E Sethe Burgie
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 46:8999-9006. 2007
    ..Indeed, the nearly 180 degrees difference in hexose orientation explains the equatorial versus axial amino transfer exhibited by DesI and PseC, respectively...
  49. ncbi request reprint Molecular structure of Saccharomyces cerevisiae Gal1p, a bifunctional galactokinase and transcriptional inducer
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 280:36905-11. 2005
    ..Understanding the manner in which two of the proteins that function in transcriptional regulation interact with one another is an important step in determining the overall molecular mechanism of this switch...
  50. pmc The catalytic mechanism of galactose mutarotase
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706 1544, USA
    Protein Sci 12:1051-9. 2003
    ..Specifically, Glu 304 serves as the active site base to initiate the reaction by removing the proton from the C-1 hydroxyl group of the sugar substrate and His 170 functions as the active site acid to protonate the C-5 ring oxygen...
  51. ncbi request reprint Kinetic and structural analysis of alpha-D-Glucose-1-phosphate cytidylyltransferase from Salmonella typhi
    Nicole M Koropatkin
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 280:10774-80. 2005
    ..The kinetic and x-ray crystallographic data presented here support a mechanism for this enzyme that is similar to that reported for the glucose-1-phosphate thymidylyltransferases...
  52. ncbi request reprint The x-ray structure of dTDP-4-keto-6-deoxy-D-glucose-3,4-ketoisomerase
    Melissa L Davis
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706 1544, USA
    J Biol Chem 282:19227-36. 2007
    ..Site-directed mutagenesis experiments, enzymatic assays, and x-ray crystallographic analyses suggest that His(49) functions as an active site base...
  53. pmc Structural and functional studies of Aspergillus clavatus N(5)-carboxyaminoimidazole ribonucleotide synthetase
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 49:752-60. 2010
    ..This intermediate subsequently decarboxylates to CO(2) and inorganic phosphate, and the amino group of AIR, through general base assistance by Asp 153, attacks CO(2) to form N(5)-CAIR...
  54. pmc Long-range allosteric transitions in carbamoyl phosphate synthetase
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, WI, 53706, USA
    Protein Sci 13:2398-405. 2004
    ..The manner in which UMP binds to carbamoyl phosphate synthetase is described...
  55. ncbi request reprint Carbamoyl-phosphate synthetase. Creation of an escape route for ammonia
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin, 53706 1544, USA
    J Biol Chem 277:39722-7. 2002
    ..The substitution also effected the disposition of several key catalytic amino acid side chains in the small subunit active site...
  56. ncbi request reprint High resolution x-ray structure of tyvelose epimerase from Salmonella typhi
    Nicole M Koropatkin
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 278:20874-81. 2003
    ..On the basis of the observed binding mode for CDP, it is possible to predict the manner in which the substrate, CDP-paratose, and the product, CDP-tyvelose, might be accommodated within the active site of tyvelose epimerase...
  57. ncbi request reprint The structural determination of an insect sterol carrier protein-2 with a ligand-bound C16 fatty acid at 1.35-A resolution
    David H Dyer
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 278:39085-91. 2003
    ..K., and Glumoff, T. (2001) J. Mol. Biol. 313, 1127-1138). The present study suggests that the binding pocket in the SCP-2 family of proteins may exhibit conformational flexibility to allow coordination of a variety of lipids...
  58. pmc The structure of GDP-4-keto-6-deoxy-D-mannose-3-dehydratase: a unique coenzyme B6-dependent enzyme
    Paul D Cook
    Department of Biochemistry, University of Wisconsin Madison, Wisconsin 53706, USA
    Protein Sci 15:2093-106. 2006
    ..Taken together, these two structures, along with previously reported biochemical data, support the role of His 188 as the active site base required for catalysis...
  59. ncbi request reprint X-ray crystallographic analyses of inhibitor and substrate complexes of wild-type and mutant 4-hydroxybenzoyl-CoA thioesterase
    James B Thoden
    Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706 1544, USA
    J Biol Chem 277:27468-76. 2002
    ..Taken together, these investigations suggest that the reaction mechanism may proceed through an acyl enzyme intermediate...
  60. ncbi request reprint The molecular structure of UDP-galactose 4-epimerase from Escherichia coli determined at 2.5 A resolution
    A J Bauer
    Department of Biochemistry, University of Wisconsin, Madison 53705
    Proteins 12:372-81. 1992
    ..Likewise, each subunit in the dimer also binds one substrate analogue...
  61. pmc Structural analysis of QdtB, an aminotransferase required for the biosynthesis of dTDP-3-acetamido-3,6-dideoxy-alpha-D-glucose
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 48:1553-61. 2009
    ..This investigation represents the first structural analysis of a sugar-modifying aminotransferase with a bound product in its active site that functions at the C-3' rather than the C-4' position of the hexose...
  62. doi request reprint Structural and functional studies of WlbA: A dehydrogenase involved in the biosynthesis of 2,3-diacetamido-2,3-dideoxy-D-mannuronic acid
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 49:7939-48. 2010
    ..The UDP-linked sugar substrate adopts a highly unusual curved conformation when bound in the WlbA active site cleft. Lys 101 and His 185 most likely play key roles in catalysis...
  63. pmc The interaction between an acidic transcriptional activator and its inhibitor. The molecular basis of Gal4p recognition by Gal80p
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 283:30266-72. 2008
    ..This investigation provides a new molecular scaffold for understanding previous biochemical and genetic studies...
  64. pmc Active site geometry of glucose-1-phosphate uridylyltransferase
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison 53706 1544, USA
    Protein Sci 16:1379-88. 2007
    ..The structure presented here provides further support for the role of the conserved magnesium ion in the catalytic mechanisms of the sugar-1-phosphate nucleotidylyltransferases...
  65. doi request reprint Molecular architecture of a C-3'-methyltransferase involved in the biosynthesis of D-tetronitrose
    Nathan A Bruender
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 49:5891-8. 2010
    ..Key residues involved in sugar binding include His 181, Glu 224, His 225, and Tyr 222. Their possible roles in catalysis are discussed...
  66. ncbi request reprint Structural analysis of the Y299C mutant of Escherichia coli UDP-galactose 4-epimerase. Teaching an old dog new tricks
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, WI 53706 1544, USA
    J Biol Chem 277:27528-34. 2002
    ..Specifically, although the Y299C mutation in the bacterial enzyme resulted in a loss of epimerase activity with regard to UDP-Gal by almost 5-fold, it resulted in a gain of activity against UDP-GalNAc by more than 230-fold...
  67. ncbi request reprint GDP-4-keto-6-deoxy-D-mannose 3-dehydratase, accommodating a sugar substrate in the active site
    Paul D Cook
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706 1544, USA
    J Biol Chem 283:4295-303. 2008
    ..Additionally, we report data revealing that wild-type ColD is able to catalyze the production of GDP-4-keto-3,6-dideoxymannose using GDP-perosamine instead of GDP-4-keto-6-deoxymannose as a substrate...
  68. doi request reprint X-ray structure of kijd3, a key enzyme involved in the biosynthesis of D-kijanose
    Nathan A Bruender
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 49:3517-24. 2010
    ..The molecular architecture of KijD3 described in this report serves as a paradigm for a new family of enzymes that function on dTDP-linked sugar substrates...
  69. ncbi request reprint PurT-encoded glycinamide ribonucleotide transformylase. Accommodation of adenosine nucleotide analogs within the active site
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 277:23898-908. 2002
    ..This sensitivity to nucleotide identity is in sharp contrast to that observed for the "P-loop"-containing enzymes, in which the conformation of the binding motif is virtually unchanged in the presence or absence of nucleotides...
  70. pmc Molecular architecture of DesV from Streptomyces venezuelae: a PLP-dependent transaminase involved in the biosynthesis of the unusual sugar desosamine
    E Sethe Burgie
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Protein Sci 16:887-96. 2007
    ..In the case of PseC, however, the amino group is transferred to the C-4 rather than the C-3 position. Details concerning the structural analysis of DesV and a comparison of its molecular architecture to that of PseC are presented...
  71. ncbi request reprint Understanding a transcriptional paradigm at the molecular level. The structure of yeast Gal80p
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 282:1534-8. 2007
    ....
  72. ncbi request reprint Evolution of enzymatic activity in the enolase superfamily: structural studies of the promiscuous o-succinylbenzoate synthase from Amycolatopsis
    James B Thoden
    Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA
    Biochemistry 43:5716-27. 2004
    ..Accommodation of the components of the N-acyl linkage appears to be the reason that this enzyme is capable of a racemization reaction on these substrates, whereas the orthologous OSBS from Escherichia coli lacks this functionality...
  73. pmc The molecular architecture of glucose-1-phosphate uridylyltransferase
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Protein Sci 16:432-40. 2007
    ..Details concerning the overall structure of UGPase and a comparison with glucose-1-phosphate thymidylyltransferase are presented...
  74. pmc Molecular structure of WlbB, a bacterial N-acetyltransferase involved in the biosynthesis of 2,3-diacetamido-2,3-dideoxy-D-mannuronic acid
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 49:4644-53. 2010
    ....
  75. pmc Structural and functional studies of QdtC: an N-acetyltransferase required for the biosynthesis of dTDP-3-acetamido-3,6-dideoxy-alpha-D-glucose
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 48:2699-709. 2009
    ..Rather, the sulfur of CoA functions as the ultimate proton acceptor...
  76. ncbi request reprint High resolution X-ray structure of dTDP-glucose 4,6-dehydratase from Streptomyces venezuelae
    Simon T M Allard
    Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA
    J Biol Chem 279:2211-20. 2004
    ..This investigation provides further detailed information for understanding the exquisite chemistry that occurs in these remarkable enzymes...
  77. ncbi request reprint Crystal structure of gene locus At3g16990 from Arabidopsis thaliana
    Paul G Blommel
    Center for Eukaryotic Structural Genomics, Department of Biochemistry, University of Wisconsin Madison, Madison, Wisconsin 53706, USA
    Proteins 57:221-2. 2004
  78. doi request reprint Three-dimensional structure of DesVI from Streptomyces venezuelae: a sugar N,N-dimethyltransferase required for dTDP-desosamine biosynthesis
    E Sethe Burgie
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 47:3982-8. 2008
    ..As such, the ternary structure of DesVI reported here serves as a structural paradigm for a new family of dimethyltransferases that function on nucleotide-linked sugars...
  79. ncbi request reprint Molecular structure of alpha-D-glucose-1-phosphate cytidylyltransferase from Salmonella typhi
    Nicole M Koropatkin
    Department of Biochemistry, University of Wisconsin, Madison 53706, USA
    J Biol Chem 279:44023-9. 2004
    ..The topology of the main core domain bears striking similarity to that observed for glucose-1-phosphate thymidylyltransferase and 4-diphosphocytidyl-2-C-methylerythritol synthetase...
  80. ncbi request reprint Structure of CDP-D-glucose 4,6-dehydratase from Salmonella typhi complexed with CDP-D-xylose
    Nicole M Koropatkin
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706 1544, USA
    Acta Crystallogr D Biol Crystallogr 61:365-73. 2005
    ....
  81. pmc A structural study of GDP-4-keto-6-deoxy-D-mannose-3-dehydratase: caught in the act of geminal diamine formation
    Paul D Cook
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 46:14215-24. 2007
    ..Functional assays further demonstrate that this mutant form of ColD cannot catalyze the dehydration reaction...
  82. ncbi request reprint The three-dimensional structure of the core domain of Naf Y from Azotobacter vinelandii determined at 1.8-A resolution
    David H Dyer
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 278:32150-6. 2003
    ..As such, this represents a new fold capable of binding FeMo-co, where the only previous example was that seen in dinitrogenase...
  83. pmc Structural analysis of the active site geometry of N5-carboxyaminoimidazole ribonucleotide synthetase from Escherichia coli
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 47:13346-53. 2008
    ..Using the information derived from the two structures reported here, coupled with molecular modeling, we propose a catalytic mechanism for N(5)-CAIR synthetase...
  84. ncbi request reprint High-resolution X-ray structure of isoaspartyl dipeptidase from Escherichia coli
    James B Thoden
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 42:4874-82. 2003
    ..This structural analysis confirms the placement of isoaspartyl dipeptidase into the urease-related amidohydrolase superfamily...
  85. ncbi request reprint Determinants of function and substrate specificity in human UDP-galactose 4'-epimerase
    Jenny M Schulz
    Graduate Program in Nutrition and Health Sciences, Emory University, Atlanta, Georgia 30322, USA
    J Biol Chem 279:32796-803. 2004
    ..Together, these results serve to validate the wild-type hGALE crystal structure and fully support the hypothesis that residue 307 acts as a gatekeeper mediating substrate access to the hGALE active site...
  86. ncbi request reprint Inactivation of the amidotransferase activity of carbamoyl phosphate synthetase by the antibiotic acivicin
    Bryant W Miles
    Department of Chemistry, Texas A and M University, College Station, Texas 77842 3012, USA
    J Biol Chem 277:4368-73. 2002
    ..The thiol group of Cys-269 was covalently attached to the dihydroisoxazole ring of acivicin with the displacement of a chloride ion...
  87. ncbi request reprint Mechanism of the reaction catalyzed by isoaspartyl dipeptidase from Escherichia coli
    Ricardo Marti-Arbona
    Department of Chemistry, P O Box 30012, Texas A and M University, College Station, Texas 77842 3012, USA
    Biochemistry 44:7115-24. 2005
    ..Collapse of the tetrahedral intermediate and cleavage of the carbon-nitrogen bond occur with donation of a proton from the protonated form of Asp285...
  88. ncbi request reprint Kinetic mechanism of asparagine synthetase from Vibrio cholerae
    Vicente Fresquet
    Department of Chemistry, Texas A and M University, PO Box 30012, College Station, TX 77843 3012, USA
    Bioorg Chem 32:63-75. 2004
    ..The rate of hydrolysis of glutamine is largely independent of the activation of aspartate and thus the reaction rates at the two active sites are essentially uncoupled from one another...
  89. ncbi request reprint Functional characterization of the K257R and G319E-hGALE alleles found in patients with ostensibly peripheral epimerase deficiency galactosemia
    Jamie Wasilenko
    Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, GA 30322, USA
    Mol Genet Metab 84:32-8. 2005
    ....
  90. ncbi request reprint Enhanced degradation of chemical warfare agents through molecular engineering of the phosphotriesterase active site
    Craig M Hill
    Department of Chemistry, P O Box 30012, Texas A and M University, College Station, TX 77842 3012, USA
    J Am Chem Soc 125:8990-1. 2003
    ..These studies demonstrate that substantial changes in substrate specificity can be achieved by relatively minor changes to the primary amino acid sequence...
  91. ncbi request reprint Enzymes with molecular tunnels
    Frank M Raushel
    Department of Chemistry, Texas A and M University, College Station, Texas 77843 3012, USA
    Acc Chem Res 36:539-48. 2003
    ..Here we describe and summarize our current understanding of molecular tunnels observed in various enzyme systems...

Research Grants26

  1. Structure-Function Analysis of Enzymes
    Hazel Holden; Fiscal Year: 2004
    ....
  2. X-ray Studies of Sugar-Modifying Enzymes
    Hazel Holden; Fiscal Year: 2005
    ..abstract_text> ..
  3. X-ray Studies of Sugar-Modifying Enzymes
    Hazel Holden; Fiscal Year: 2010
    ..Taken together, these studies will provide new information with respect to both sugar metabolism and eukaryotic transcriptional regulation. ..
  4. STRUCTURAL STUDIES OF NUCLEOTIDE DEPENDENT ENZYMES
    Hazel Holden; Fiscal Year: 2001
    ..Taken together, these studies will provide a detailed description of the role of nucleotides in the enzymatic functions of these proteins. ..
  5. STRUCTURE/FUNCTION ANALYSIS OF ENZYMES
    Hazel Holden; Fiscal Year: 2000
    ....
  6. X-ray Studies of Sugar-Modifying Enzymes
    Hazel Holden; Fiscal Year: 2010
    ..Taken together, these studies will provide new information with respect to both sugar metabolism and eukaryotic transcriptional regulation. ..