T P Begley

Summary

Affiliation: Cornell University
Country: USA

Publications

  1. ncbi request reprint The structural basis for the remarkable catalytic proficiency of orotidine 5'-monophosphate decarboxylase
    T P Begley
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Curr Opin Struct Biol 10:711-8. 2000
  2. ncbi request reprint Cofactor biosynthesis: an organic chemist's treasure trove
    Tadhg P Begley
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Nat Prod Rep 23:15-25. 2006
  3. ncbi request reprint Enzymatic reactions involving novel mechanisms of carbanion stabilization
    Tadhg P Begley
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, NY14853, USA
    Curr Opin Chem Biol 8:508-15. 2004
  4. ncbi request reprint The enzymology of sulfur activation during thiamin and biotin biosynthesis
    T P Begley
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Curr Opin Chem Biol 3:623-9. 1999
  5. ncbi request reprint Thiamin biosynthesis in prokaryotes
    T P Begley
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Arch Microbiol 171:293-300. 1999
  6. pmc Cofactor biosynthesis--still yielding fascinating new biological chemistry
    Tadhg P Begley
    Cornell University, Department of Chemistry and Chemical Biology, 120 Baker Lab, Ithaca, NY 14853, United States
    Curr Opin Chem Biol 12:118-25. 2008
  7. ncbi request reprint Chemical biology: an educational challenge for chemistry departments
    Tadhg P Begley
    Department of Chemistry and Chemical Biology, Cornell University, 120 Baker Laboratory, Ithaca, New York 14853, USA
    Nat Chem Biol 1:236-8. 2005
  8. ncbi request reprint The mechanism of action of bacimethrin, a naturally occurring thiamin antimetabolite
    J J Reddick
    Department of Chemistry and Chemical Biology, Cornell University, Baker Laboratory, Ithaca, NY 14853, USA
    Bioorg Med Chem Lett 11:2245-8. 2001
  9. ncbi request reprint Structural characterization of the enzyme-substrate, enzyme-intermediate, and enzyme-product complexes of thiamin phosphate synthase
    D H Peapus
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 40:10103-14. 2001
  10. pmc Efficient sequence analysis of the six gene products (7-74 kDa) from the Escherichia coli thiamin biosynthetic operon by tandem high-resolution mass spectrometry
    N L Kelleher
    Department of Chemistry, Cornell University, Ithaca, New York 14853 1301, USA
    Protein Sci 7:1796-801. 1998

Research Grants

  1. CHEMISTRY OF BIOLOGICAL SYSTEMS
    Tadhg Begley; Fiscal Year: 2007

Collaborators

  • Steven Ealick
  • Erick Strauss
  • C Wang
  • J Lee
  • Y Zhang
  • Q Hao
  • MARTHA STIPANUK
  • Kathrin Breuker
  • Qingqiu Huang
  • BRIAN CRANE
  • Fred W McLafferty
  • Stephen W Ragsdale
  • Jason J Reddick
  • Aimin Liu
  • C Wrenger
  • Diana Downs
  • Ghislain Schyns
  • Abhishek Chatterjee
  • Jeremiah W Hanes
  • Pieter C Dorrestein
  • Kathryn M McCulloch
  • Huili Zhai
  • Tathagata Mukherjee
  • Joo Heon Park
  • Christopher T Jurgenson
  • Cynthia Kinsland
  • Kristin E Burns
  • Brian G Lawhorn
  • Guangxing Sun
  • Ying Ge
  • C Kinsland
  • Ethan C Settembre
  • Frank C Schroeder
  • Christopher J Fecko
  • H J Chiu
  • Amy L Haas
  • Amrita Hazra
  • Seán E O'Leary
  • Ivan Keresztes
  • Erika V Soriano
  • Amy L Jenkins
  • Amy M Godert
  • Amy Haas Jenkins
  • Watt W Webb
  • Christopher Lehmann
  • Chad R Simmons
  • N L Kelleher
  • Fairuz Zein
  • S V Taylor
  • N Campobasso
  • Kristin Burns
  • Angela V Toms
  • Pieter Dorrestein
  • Keri L Colabroy
  • Jonathan Melnick
  • Jacob A Bauer
  • Andrei Osterman
  • Jonathan S Melnick
  • Javier Seravalli
  • Ethan Settembre
  • Narayanan Manoj
  • Eric M Bennett
  • Oleg Kurnasov
  • Ruchi Anand
  • Gong Cheng
  • D H Peapus
  • J Xi
  • R A Mehl
  • Sameh Abdelwahed
  • T C Appleby
  • Shridhar Bale
  • Kanagalaghatta R Rajashankar
  • David G Hilmey
  • Sébastien Potot
  • John T Lis
  • Clifford E Kraft
  • Mi Jin
  • Katherine M Munson
  • Abbie Saunders
  • Robert B Nicewonger
  • Xuemei Han
  • Qun Liu
  • You Na Kang
  • P Andrew Karplus
  • Sabine Baumgart
  • Nathan P Laun
  • Tingfeng Li
  • Yun Xiang
  • Cynthia L Kinsland
  • Ewa Lis

Detail Information

Publications86

  1. ncbi request reprint The structural basis for the remarkable catalytic proficiency of orotidine 5'-monophosphate decarboxylase
    T P Begley
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Curr Opin Struct Biol 10:711-8. 2000
    ....
  2. ncbi request reprint Cofactor biosynthesis: an organic chemist's treasure trove
    Tadhg P Begley
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Nat Prod Rep 23:15-25. 2006
  3. ncbi request reprint Enzymatic reactions involving novel mechanisms of carbanion stabilization
    Tadhg P Begley
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, NY14853, USA
    Curr Opin Chem Biol 8:508-15. 2004
    ....
  4. ncbi request reprint The enzymology of sulfur activation during thiamin and biotin biosynthesis
    T P Begley
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Curr Opin Chem Biol 3:623-9. 1999
    ..This radical is formed by the reductive cleavage of S-adenosylmethionine by the reduced Fe-S cluster of biotin synthase...
  5. ncbi request reprint Thiamin biosynthesis in prokaryotes
    T P Begley
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Arch Microbiol 171:293-300. 1999
    ..The specific reactions catalyzed by ThiC (pyrimidine formation), and ThiGH and ThiI (thiazole formation) have not yet been identified...
  6. pmc Cofactor biosynthesis--still yielding fascinating new biological chemistry
    Tadhg P Begley
    Cornell University, Department of Chemistry and Chemical Biology, 120 Baker Lab, Ithaca, NY 14853, United States
    Curr Opin Chem Biol 12:118-25. 2008
    ..This mini review covers recent advances in the mechanistic enzymology of cofactor biosynthesis...
  7. ncbi request reprint Chemical biology: an educational challenge for chemistry departments
    Tadhg P Begley
    Department of Chemistry and Chemical Biology, Cornell University, 120 Baker Laboratory, Ithaca, New York 14853, USA
    Nat Chem Biol 1:236-8. 2005
    ..Chemical biology, broadly defined as the application of chemistry to the study of molecular events in biological systems, presents an opportunity for the reorganization and revitalization of the chemistry curriculum...
  8. ncbi request reprint The mechanism of action of bacimethrin, a naturally occurring thiamin antimetabolite
    J J Reddick
    Department of Chemistry and Chemical Biology, Cornell University, Baker Laboratory, Ithaca, NY 14853, USA
    Bioorg Med Chem Lett 11:2245-8. 2001
    ..Bacimethrin does not cause repression of the genes coding for the thiamin biosynthetic enzymes...
  9. ncbi request reprint Structural characterization of the enzyme-substrate, enzyme-intermediate, and enzyme-product complexes of thiamin phosphate synthase
    D H Peapus
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 40:10103-14. 2001
    ....
  10. pmc Efficient sequence analysis of the six gene products (7-74 kDa) from the Escherichia coli thiamin biosynthetic operon by tandem high-resolution mass spectrometry
    N L Kelleher
    Department of Chemistry, Cornell University, Ithaca, New York 14853 1301, USA
    Protein Sci 7:1796-801. 1998
    ..74 (ThiS) and 26,896.5 Da (ThiG); MS/MS uncovered three reading frame errors and a stop codon for the first protein. MS/MS ions are consistent with 68 fragments predicted by the corrected ThiS/ThiG DNA sequences...
  11. ncbi request reprint Thiamin biosynthesis in Escherichia coli. Identification of ThiS thiocarboxylate as the immediate sulfur donor in the thiazole formation
    S V Taylor
    Department of Chemistry, Cornell University, Baker Laboratory, Ithaca, New York 14853, USA
    J Biol Chem 273:16555-60. 1998
    ..ThiF catalyzes the adenylation by ATP of the carboxyl-terminal glycine of ThiS. This reaction is likely to be involved in the activation of ThiS for sulfur transfer from cysteine or from a cysteine-derived sulfur donor...
  12. pmc Biosynthesis of the thiazole moiety of thiamin in Escherichia coli: identification of an acyldisulfide-linked protein--protein conjugate that is functionally analogous to the ubiquitin/E1 complex
    J Xi
    Department of Chemistry and Chemical Biology, Cornell University, 120 Baker Laboratory, Ithaca, NY 14853, USA
    Proc Natl Acad Sci U S A 98:8513-8. 2001
    ..This protein conjugate is also an example of an ubiquitin-E1 like protein-protein conjugate in prokaryotes and supports a strong evolutionary link between thiamin biosynthesis and the ubiquitin conjugating system...
  13. pmc Overexpression of recombinant proteins with a C-terminal thiocarboxylate: implications for protein semisynthesis and thiamin biosynthesis
    C Kinsland
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Protein Sci 7:1839-42. 1998
    ..The utility of this method for protein semisynthesis and implications for studies on the biosynthesis of thiamin are discussed...
  14. ncbi request reprint Crystal structure of thiamin phosphate synthase from Bacillus subtilis at 1.25 A resolution
    H J Chiu
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 38:6460-70. 1999
    ....
  15. ncbi request reprint Solution structure of ThiS and implications for the evolutionary roots of ubiquitin
    C Wang
    Department of Molecular Biology and Genetics, 239 Biotechnology Building, Cornell University, Ithaca, New York 14853, USA
    Nat Struct Biol 8:47-51. 2001
    ..Comparison with surface features of ubiquitin and ubiquitin homologs SUMO-1, RUB-1 and NEDD8 suggest how Nature has utilized this single fold to incorporate similar chemistry into a broad array of highly specific biological processes...
  16. ncbi request reprint Phosphopantothenoylcysteine synthetase from Escherichia coli. Identification and characterization of the last unidentified coenzyme A biosynthetic enzyme in bacteria
    E Strauss
    Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York, 14853, USA
    J Biol Chem 276:13513-6. 2001
    ..This discovery completes the identification of all the enzymes involved in the biosynthesis of coenzyme A in bacteria...
  17. pmc The crystal structure and mechanism of orotidine 5'-monophosphate decarboxylase
    T C Appleby
    Department of Chemistry, Cornell University, Ithaca, NY 14853, USA
    Proc Natl Acad Sci U S A 97:2005-10. 2000
    ..We propose that the decarboxylation of OMP proceeds by an electrophilic substitution mechanism in which decarboxylation and carbon-carbon bond protonation by Lys62 occur in a concerted reaction...
  18. ncbi request reprint Crystal structure of 4-methyl-5-beta-hydroxyethylthiazole kinase from Bacillus subtilis at 1.5 A resolution
    N Campobasso
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 39:7868-77. 2000
    ....
  19. pmc Structural genes for thiamine biosynthetic enzymes (thiCEFGH) in Escherichia coli K-12
    P B Vander Horn
    Department of Chemistry, Cornell University, Ithaca, New York 14853
    J Bacteriol 175:982-92. 1993
    ..These mutants did not respond to 1-deoxy-D-threo-2-pentulose, indicating that they are blocked in the conversion of this precursor compound to the thiazole itself...
  20. pmc Characterization of the Bacillus subtilis thiC operon involved in thiamine biosynthesis
    Y Zhang
    Department of Chemistry, Cornell University, Ithaca, New York 14853, USA
    J Bacteriol 179:3030-5. 1997
    ..Transcription of the thiC operon is not regulated by thiamine or 2-methyl-4-amino-5-hydroxymethylpyrimidine and is only slightly repressed by 4-methyl-5-(beta-hydroxyethyl)thiazole...
  21. pmc Identification of the Escherichia coli nicotinic acid mononucleotide adenylyltransferase gene
    R A Mehl
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Bacteriol 182:4372-4. 2000
    ..The rate of adenylation of nicotinate mononucleotide is at least 20 times faster than the rate of adenylation of nicotinamide mononucleotide...
  22. ncbi request reprint Two-dimensional mass spectrometry of biomolecules at the subfemtomole level
    F W McLafferty
    Baker Chemistry Laboratory, Cornell University, Ithaca, NY 14853 1301, USA
    Curr Opin Chem Biol 2:571-8. 1998
    ..Selecting a specific molecular species, its two-dimensional spectrum indicates the part of the molecule that is modified; a three-dimensional spectrum of that fragment further isolates the modification site...
  23. ncbi request reprint The biosynthesis of coenzyme A in bacteria
    T P Begley
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, USA
    Vitam Horm 61:157-71. 2001
    ..Adenylation and phosphorylation of 4'-phosphopantetheine completes the biosynthesis of coenzyme A. This review will focus on the mechanistic enzymology of coenzyme A biosynthesis in bacteria...
  24. ncbi request reprint Mechanistic studies on thiamin phosphate synthase: evidence for a dissociative mechanism
    J J Reddick
    Department of Chemistry and Chemical Biology, 120 Baker Laboratory, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 40:10095-102. 2001
    ....
  25. ncbi request reprint The biosynthesis of nicotinamide adenine dinucleotides in bacteria
    T P Begley
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, USA
    Vitam Horm 61:103-19. 2001
    ..Adenylation of this mononucleotide followed by amide formation completes the biosynthesis of NAD. An additional phosphorylation gives NADP. This review focuses on the mechanistic enzymology of this pathway in bacteria...
  26. ncbi request reprint Top-down MS, a powerful complement to the high capabilities of proteolysis proteomics
    Fred W McLafferty
    Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, NY 14853, USA
    FEBS J 274:6256-68. 2007
    ....
  27. pmc Mutagenesis studies on TenA: a thiamin salvage enzyme from Bacillus subtilis
    Amy L Jenkins
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Bioorg Chem 36:29-32. 2008
    ..Catalytic roles for each of the active site residues are identified and a mechanism for the reaction is described...
  28. pmc Gene identification and structural characterization of the pyridoxal 5'-phosphate degradative protein 3-hydroxy-2-methylpyridine-4,5-dicarboxylate decarboxylase from mesorhizobium loti MAFF303099
    Tathagata Mukherjee
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 46:13606-15. 2007
    ..The structural studies described here suggest that catalysis of such decarboxylations proceeds by an aldolase-like mechanism...
  29. ncbi request reprint Structure of oxalate decarboxylase from Bacillus subtilis at 1.75 A resolution
    Ruchi Anand
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 41:7659-69. 2002
    ..Mutation of Glu333 to alanine reduces the catalytic activity by a factor of 25. The function of the other domain in oxalate decarboxylase is not yet known...
  30. doi request reprint Trapping of a chromophoric intermediate in the Pdx1-catalyzed biosynthesis of pyridoxal 5'-phosphate
    Jeremiah W Hanes
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Angew Chem Int Ed Engl 47:2102-5. 2008
  31. ncbi request reprint Structural studies on 3-hydroxyanthranilate-3,4-dioxygenase: the catalytic mechanism of a complex oxidation involved in NAD biosynthesis
    Yang Zhang
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 44:7632-43. 2005
    ..On the basis of the crystal structures of HAD, mutagenesis studies were carried out in order to elucidate the enzyme mechanism. In addition, a new mechanism for the enzyme inactivation by 4-chloro-3-hydroxyanthranilate is proposed...
  32. ncbi request reprint Comparison of femtosecond laser and continuous wave UV sources for protein-nucleic acid crosslinking
    Christopher J Fecko
    School of Applied and Engineering Physics, Cornell University, Ithaca, NY, USA
    Photochem Photobiol 83:1394-404. 2007
    ..Unfortunately, these results disprove earlier assertions that femtosecond pulsed laser sources provide significant advantages over CW radiation for protein-nucleic acid crosslinking...
  33. ncbi request reprint Crystal structure of mammalian cysteine dioxygenase. A novel mononuclear iron center for cysteine thiol oxidation
    Chad R Simmons
    Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853 8001, USA
    J Biol Chem 281:18723-33. 2006
    ....
  34. ncbi request reprint Stereochemical studies on phosphopantothenoylcysteine decarboxylase from Escherichia coli
    Erick Strauss
    Department of Chemistry and Chemical Biology, Cornell University, Baker Laboratory, Ithaca, NY 14853, USA
    Bioorg Med Chem Lett 13:339-42. 2003
    ..Our results show that the decarboxylation proceeds with retention of stereochemistry, and that the pro-R proton at C(beta) of the cysteine moiety of 2 is removed during a reversible oxidation of the thiol to a thioaldehyde intermediate...
  35. ncbi request reprint Thiamin biosynthesis in Bacillus subtilis: structure of the thiazole synthase/sulfur carrier protein complex
    Ethan C Settembre
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 43:11647-57. 2004
    ..Comparison of the ThiS binding surface to the surface of ubiquitin identified a conserved hydrophobic patch of unknown function on ubiquitin that may be involved in complex formation between ubiquitin and one of its binding partners...
  36. pmc Structure of the PLP degradative enzyme 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase from Mesorhizobium loti MAFF303099 and its mechanistic implications
    Kathryn M McCulloch
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 48:4139-49. 2009
    ..1 A using SAD phasing with and without the substrate MHPC bound. These crystal structures provide insight into the reaction mechanism and suggest roles for active site residues in the catalysis of a novel oxidative ring-opening reaction...
  37. ncbi request reprint Crystal structure of 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase from Salmonella typhimurium at 2.3 A resolution
    Gong Cheng
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Structure 10:225-35. 2002
    ..We propose that the active site accommodates the two separate reactions by providing two different binding modes for the phosphate group of HMP phosphate...
  38. ncbi request reprint Structure of human phosphopantothenoylcysteine synthetase at 2.3 A resolution
    Narayanan Manoj
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Structure 11:927-36. 2003
    ..The structure predicts a ping pong mechanism with initial formation of an acyladenylate intermediate, followed by release of pyrophosphate and attack by cysteine to form the final products PPC and AMP...
  39. doi request reprint Structural studies of thiamin monophosphate kinase in complex with substrates and products
    Kathryn M McCulloch
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 47:3810-21. 2008
    ..The structure of ThiL is compared to those of PurM, PurL, and HypE, and the ATP binding site is compared to that of PurL, for which nucleotide complexes are available...
  40. pmc Structure determination and characterization of the vitamin B6 degradative enzyme (E)-2-(acetamidomethylene)succinate hydrolase
    Kathryn M McCulloch
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 49:1226-35. 2010
    ..The structure also provides insight into the mechanism of hydrolysis of E-2AMS and identifies several potential catalytically important residues...
  41. ncbi request reprint DNA-protein cross-linking: model systems for pyrimidine-aromatic amino acid cross-linking
    Guangxing Sun
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Org Lett 8:681-3. 2006
    ..The quantum yields for the model cross-linking reactions were 18-46 times smaller than those for thymine dimer formation. Biphotonic excitation contributes little to the yield of these reactions...
  42. ncbi request reprint Biosynthesis of thiamin thiazole: determination of the regiochemistry of the S/O acyl shift by using 1,4-dideoxy-D-xylulose-5-phosphate
    Abhishek Chatterjee
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Angew Chem Int Ed Engl 45:3507-10. 2006
  43. pmc Biosynthesis of the thiamin thiazole in Bacillus subtilis: identification of the product of the thiazole synthase-catalyzed reaction
    Amrita Hazra
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Am Chem Soc 131:3225-9. 2009
    ..In this paper, we describe an optimized reconstitution of the thiamin thiazole synthase (ThiG) catalyzed reaction and demonstrate that the enzymatic product is an unanticipated dearomatized thiazole tautomer...
  44. pmc Structural insights into the mechanism of the PLP synthase holoenzyme from Thermotoga maritima
    Fairuz Zein
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 45:14609-20. 2006
    ..This channel is similar to one found in imidazole glycerol phosphate synthase; however, when the beta-barrels of the two complexes are superimposed, the glutaminase domains are rotated by about 180 degrees with respect to each other...
  45. ncbi request reprint Crystal structure and mechanism of tryptophan 2,3-dioxygenase, a heme enzyme involved in tryptophan catabolism and in quinolinate biosynthesis
    Yang Zhang
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 46:145-55. 2007
    ..Modeling of the putative (S)-tryptophan hydroperoxide intermediate into the active site, as well as substrate analogue and mutagenesis studies, are consistent with a Criegee mechanism for the reaction...
  46. doi request reprint Structural similarities between thiamin-binding protein and thiaminase-I suggest a common ancestor
    Erika V Soriano
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 47:1346-57. 2008
    ..A comparison of TbpA and thiaminase-I, a thiamin-degrading enzyme, revealed structural similarity between the two proteins, especially in domain 1, suggesting that the two proteins evolved from a common ancestor...
  47. pmc Thiamin phosphate synthase: the rate of pyrimidine carbocation formation
    Jeremiah W Hanes
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Am Chem Soc 129:4860-1. 2007
  48. ncbi request reprint Biosynthesis of the thiamin-thiazole in eukaryotes: identification of a thiazole tautomer intermediate
    Abhishek Chatterjee
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Am Chem Soc 130:11394-8. 2008
    ..Its identification provides an additional molecular snapshot of the complex reaction sequence catalyzed by the eukaryotic thiazole synthase and identifies the final step of the thiamin-thiazole biosynthesis...
  49. pmc An assay for thiaminase I in complex biological samples
    Jeremiah W Hanes
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Anal Biochem 368:33-8. 2007
    ..In addition, the assay is optimized for high-throughput analysis in a 96-well format with complex biological samples...
  50. ncbi request reprint A new thiamin salvage pathway
    Amy Haas Jenkins
    Department of Chemistry and Chemical Biology, 120 Baker Laboratory, Cornell University, Ithaca, New York 14853, USA
    Nat Chem Biol 3:492-7. 2007
    ..To our knowledge this is the first example of a thiamin salvage pathway involving thiamin analogs generated by degradation of one of the heterocyclic rings of the cofactor...
  51. ncbi request reprint 13C NMR snapshots of the complex reaction coordinate of pyridoxal phosphate synthase
    Jeremiah W Hanes
    Department of Chemistry and Chemical Biology, Cornell University, 120 Baker Laboratory, Ithaca, New York 14853, USA
    Nat Chem Biol 4:425-30. 2008
    ..This analysis revealed a new 1,5 migration of the lysine amine linking the intermediate to the enzyme during the conversion of ribose 5-phosphate to pyridoxal 5'-phosphate...
  52. pmc Catalysis of a flavoenzyme-mediated amide hydrolysis
    Tathagata Mukherjee
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Am Chem Soc 132:5550-1. 2010
    ..This study further illustrates the extraordinary catalytic versatility of the flavin cofactor...
  53. pmc Thiamin biosynthesis in eukaryotes: characterization of the enzyme-bound product of thiazole synthase from Saccharomyces cerevisiae and its implications in thiazole biosynthesis
    Abhishek Chatterjee
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Am Chem Soc 128:7158-9. 2006
    ..The unexpected structure of this compound yields the first insights into the mechanism of thiamin thiazole biosynthesis in eukaryotes...
  54. pmc Structure of the Escherichia coli ThiS-ThiF complex, a key component of the sulfur transfer system in thiamin biosynthesis
    Christopher Lehmann
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 45:11-9. 2006
    ..The ThiF-ThiS structure clarifies the mechanism of the sulfur transfer chemistry involved in thiazole biosynthesis...
  55. ncbi request reprint The biosynthesis of the thiazole phosphate moiety of thiamin (vitamin B1): the early steps catalyzed by thiazole synthase
    Pieter C Dorrestein
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Am Chem Soc 126:3091-6. 2004
    ..This mechanism involves the generation of a ketone at C3 of DXP by an Amadori-type rearrangement of the imine followed by nucleophillic addition of the sulfur carrier protein (ThiS-thiocarboxylate) to this carbonyl group...
  56. ncbi request reprint Structural biology of enzymes of the thiamin biosynthesis pathway
    Ethan Settembre
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14850, USA
    Curr Opin Struct Biol 13:739-47. 2003
    ..Structural and mechanistic studies on thiamin biosynthetic enzymes have played a key role in increasing our understanding of thiamin pyrophosphate biosynthesis and have revealed unexpected evolutionary ties...
  57. ncbi request reprint Structural characterization of the regulatory proteins TenA and TenI from Bacillus subtilis and identification of TenA as a thiaminase II
    Angela V Toms
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 44:2319-29. 2005
    ..The structure suggests that TenI is unable to bind thiamin phosphate, largely resulting from the presence of leucine at position 119, while the corresponding residue in thiamin phosphate synthase is glycine...
  58. ncbi request reprint The biosynthesis of the thiazole phosphate moiety of thiamin: the sulfur transfer mediated by the sulfur carrier protein ThiS
    Pieter C Dorrestein
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Chem Biol 11:1373-81. 2004
    ..These observations further clarify the mechanism of the complex thiazole biosynthesis in bacteria...
  59. ncbi request reprint Three-dimensional structure of YaaE from Bacillus subtilis, a glutaminase implicated in pyridoxal-5'-phosphate biosynthesis
    Jacob A Bauer
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Biol Chem 279:2704-11. 2004
    ..This model predicts that the ammonia molecule generated by YaaE is channeled through the center of the YaaD barrel to the putative YaaD active site...
  60. ncbi request reprint Oxidative cascades: a facile biosynthetic strategy for the assembly of complex molecules
    Pieter Dorrestein
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Bioorg Chem 33:136-48. 2005
    ..This review will describe the application of this motif to the synthesis of dimethylbenzimidazole, pyoverdine, actinomycin, cystodytin, pyrroloquinoline quinone, and the cataract pigment...
  61. ncbi request reprint Top down characterization of secreted proteins from Mycobacterium tuberculosis by electron capture dissociation mass spectrometry
    Ying Ge
    Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, NY 14853 1301, USA
    J Am Soc Mass Spectrom 14:253-61. 2003
    ..Although in eubacteria the latter is relatively rare, a 9 kDa protein showed 7 hexose attachments and two 20 kDa proteins each had 20 attachments. For MS/MS, electron capture dissociation was especially effective...
  62. ncbi request reprint Structural and mechanistic studies on ThiO, a glycine oxidase essential for thiamin biosynthesis in Bacillus subtilis
    Ethan C Settembre
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 42:2971-81. 2003
    ..The ThiO structure, as well as the observation that N-cyclopropylglycine is a good substrate, supports a hydride transfer mechanism for the enzyme. A mechanistic proposal for the role of ThiO in thiazole biosynthesis is also described...
  63. ncbi request reprint Top down characterization of larger proteins (45 kDa) by electron capture dissociation mass spectrometry
    Ying Ge
    Baker Laboratory, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853 1301, USA
    J Am Chem Soc 124:672-8. 2002
    ..The addition of ECD substantially increases the capabilities of top down FTMS for the detailed structural characterization of large proteins...
  64. ncbi request reprint Thi20, a remarkable enzyme from Saccharomyces cerevisiae with dual thiamin biosynthetic and degradation activities
    Amy L Haas
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Bioorg Chem 33:338-44. 2005
    ..This demonstrates that Thi20 is a trifunctional protein with thiamin biosynthetic and degradative activity...
  65. pmc Reconstitution of a new cysteine biosynthetic pathway in Mycobacterium tuberculosis
    Kristin E Burns
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Am Chem Soc 127:11602-3. 2005
    ..Mec+ contains a JAMM motif, and this work provides the first functional characterization of the JAMM motif in prokaryotes. MoeZ, a paralogue of ThiF, has been shown to transfer sulfur onto CysO...
  66. ncbi request reprint Mechanistic studies on phosphopantothenoylcysteine decarboxylase: trapping of an enethiolate intermediate with a mechanism-based inactivating agent
    Erick Strauss
    Department of Chemistry, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa
    Biochemistry 43:15520-33. 2004
    ....
  67. pmc Identification of the two missing bacterial genes involved in thiamine salvage: thiamine pyrophosphokinase and thiamine kinase
    Jonathan Melnick
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Bacteriol 186:3660-2. 2004
    ..The genes encoding thiamine kinase in Escherichia coli (ycfN) and thiamine pyrophosphokinase in Bacillus subtilis (yloS) have been identified. This study completes the identification of the thiamine salvage enzymes in bacteria...
  68. ncbi request reprint An efficient enzymatic synthesis of thiamin pyrophosphate
    Jonathan S Melnick
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14850, USA
    Bioorg Med Chem Lett 13:4139-41. 2003
    ..This provides a facile route to isotopically labeled thiamin pyrophosphate from its readily available pyrimidine and thiazole precursors...
  69. ncbi request reprint A genetic screen for the identification of thiamin metabolic genes
    Brian G Lawhorn
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Biol Chem 279:43555-9. 2004
    ..The gene products YmfB and Cof catalyze the hydrolysis of 4-amino-2-methyl-5-hydroxymethylpyrimidine pyrophosphate to 4-amino-2-methyl-5-hydroxymethylpyrimidine phosphate. YmfB also converts thiamin pyrophosphate into thiamin phosphate...
  70. ncbi request reprint The selectivity for cysteine over serine in coenzyme A biosynthesis
    Erick Strauss
    Department of Chemistry, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa
    Chembiochem 6:284-6. 2005
  71. ncbi request reprint Biosynthesis of the thiamin pyrimidine: the reconstitution of a remarkable rearrangement reaction
    Brian G Lawhorn
    Baker Laboratory, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Org Biomol Chem 2:2538-46. 2004
    ..Labeling studies to determine the origin of most of the atoms in the pyrimidine are described. Based on these studies, a new mechanism for HMP formation is proposed...
  72. ncbi request reprint Simultaneous kinetic characterization of multiple protein forms by top down mass spectrometry
    Huili Zhai
    Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853 1301, USA
    J Am Soc Mass Spectrom 16:1052-9. 2005
    ..Stable intermediates with different SS bonding (same molecular weight) can be differentiated by MS/MS, while molecular ions differing by only 2 Da are distinguished clearly by synthesizing isotopically depleted proteins...
  73. ncbi request reprint The antibiotic activity of N-pentylpantothenamide results from its conversion to ethyldethia-coenzyme a, a coenzyme a antimetabolite
    Erick Strauss
    Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York, 14853, USA
    J Biol Chem 277:48205-9. 2002
    ..We conclude that the mechanism of toxicity of N-pentylpantothenamide is most likely due to its biosynthetic conversion to the CoA analog ethyldethia-CoA, which may act as an inhibitor of CoA- and acetyl-CoA-utilizing enzymes...
  74. pmc Functional copper at the acetyl-CoA synthase active site
    Javier Seravalli
    Department of Biochemistry, University of Nebraska, Lincoln, NE 68588, USA
    Proc Natl Acad Sci U S A 100:3689-94. 2003
    ..4-A Se-Cu bond, strongly implicating a Cu-SCoA intermediate in the mechanism of acetyl-CoA synthesis. These results indicate an essential and functional role for copper in the CODH/ACS from acetogenic and methanogenic organisms...
  75. pmc O-phospho-L-serine and the thiocarboxylated sulfur carrier protein CysO-COSH are substrates for CysM, a cysteine synthase from Mycobacterium tuberculosis
    Seán E O'Leary
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853 1301, USA
    Biochemistry 47:11606-15. 2008
    ..This study represents the first detailed kinetic characterization of sulfide transfer from a sulfide carrier protein...
  76. ncbi request reprint Vitamin B1 de novo synthesis in the human malaria parasite Plasmodium falciparum depends on external provision of 4-amino-5-hydroxymethyl-2-methylpyrimidine
    Carsten Wrenger
    Department of Biochemistry, Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Strasse 74, D 20359 Hamburg, Germany
    Biol Chem 387:41-51. 2006
    ..These results demonstrate that the human malaria parasite P. falciparum possesses active vitamin B1 biosynthesis, which depends on external provision of thiamine precursors...
  77. ncbi request reprint The mechanism of inactivation of 3-hydroxyanthranilate-3,4-dioxygenase by 4-chloro-3-hydroxyanthranilate
    Keri L Colabroy
    Department of Chemistry and Chemical Biology, 120 Baker Laboratory, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 44:7623-31. 2005
    ..These results are consistent with a mechanism in which the enzyme, complexed to the inhibitor and O2, generates superoxide which subsequently dissociates, leaving the inhibitor and the oxidized iron center at the active site...
  78. ncbi request reprint Biosynthesis of the thiazole moiety of thiamin pyrophosphate (vitamin B1)
    Joo Heon Park
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    Biochemistry 42:12430-8. 2003
    ....
  79. ncbi request reprint Reconstitution and biochemical characterization of a new pyridoxal-5'-phosphate biosynthetic pathway
    Kristin E Burns
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Am Chem Soc 127:3682-3. 2005
    ..The substrates for Bacillus subtilis PLP synthase (YaaD and YaaE) are identified, and the first reconstitution of PLP biosynthesis using this pathway is described. Three partial reactions catalyzed by YaaD are also identified...
  80. doi request reprint Mechanistic studies on pyridoxal phosphate synthase: the reaction pathway leading to a chromophoric intermediate
    Jeremiah W Hanes
    Department of Chemistry and Chemical Biology, 120 Baker Laboratory, Cornell University, Ithaca, New York 14853, USA
    J Am Chem Soc 130:3043-52. 2008
    ..These results allow us to narrow the mechanistic possibilities for the complex series of reactions involved in PLP formation...
  81. ncbi request reprint Structural insights into the function of the thiamin biosynthetic enzyme Thi4 from Saccharomyces cerevisiae
    Christopher T Jurgenson
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853 1301, USA
    Biochemistry 45:11061-70. 2006
    ..Additionally, the Thi4 structure reveals the first protein structure with a GR(2) domain that binds NAD instead of FAD, raising interesting questions about how this protein evolved from a flavoenzyme to a NAD binding enzyme...
  82. ncbi request reprint NAD biosynthesis: identification of the tryptophan to quinolinate pathway in bacteria
    Oleg Kurnasov
    Integrated Genomics, 2201 West Campbell Park Drive, Chicago, IL 60612, USA
    Chem Biol 10:1195-204. 2003
    ..Representative examples of each of these genes were overexpressed, and the predicted functions are confirmed in each case using unambiguous biochemical assays...
  83. pmc Characterization of two kinases involved in thiamine pyrophosphate and pyridoxal phosphate biosynthesis in Bacillus subtilis: 4-amino-5-hydroxymethyl-2methylpyrimidine kinase and pyridoxal kinase
    Joo Heon Park
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Bacteriol 186:1571-3. 2004
    ..subtilis ThiD has pyridoxine, pyridoxal, and pyridoxamine kinase activity and should be reannotated PdxK...
  84. pmc Biosynthesis of the thioquinolobactin siderophore: an interesting variation on sulfur transfer
    Amy M Godert
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    J Bacteriol 189:2941-4. 2007
    ..A JAMM motif protein cleaves the C-terminal amino acid residues following a diglycine moiety on a small sulfur carrier protein, and the modified C terminus is activated and sulfurylated, forming a thiocarboxylate...
  85. ncbi request reprint Biochemistry: molecular cannibalism
    Steven E Ealick
    Nature 446:387-8. 2007
  86. pmc Biosynthesis of thiamin thiazole in eukaryotes: conversion of NAD to an advanced intermediate
    Abhishek Chatterjee
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Am Chem Soc 129:2914-22. 2007
    ..These observations confirm NAD as the substrate for THI4 and elucidate the early steps of this unique biosynthesis of the thiazole moiety of thiamin in eukaryotes...

Research Grants3

  1. CHEMISTRY OF BIOLOGICAL SYSTEMS
    Tadhg Begley; Fiscal Year: 2007
    ..Secondly, trainees are required to participate in internships in biotech, life science, or pharmaceutical companies, through which they gain exposure to, and experience in, interdisciplinary biomedical research. ..