L Tong

Summary

Affiliation: Columbia University
Country: USA

Publications

  1. ncbi request reprint How to take advantage of non-crystallographic symmetry in molecular replacement: 'locked' rotation and translation functions
    L Tong
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Acta Crystallogr D Biol Crystallogr 57:1383-9. 2001
  2. ncbi request reprint Pyrazole urea-based inhibitors of p38 MAP kinase: from lead compound to clinical candidate
    John Regan
    Department of Medicinal Chemistry, Research and Development Center, Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877, USA
    J Med Chem 45:2994-3008. 2002
  3. ncbi request reprint Crystal structures of substrate complexes of malic enzyme and insights into the catalytic mechanism
    Xiao Tao
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Structure 11:1141-50. 2003
  4. pmc Structure and function of the phenazine biosynthetic protein PhzF from Pseudomonas fluorescens
    Wulf Blankenfeldt
    Max Planck Institute of Molecular Physiology, Otto Hahn Strasse 11, 44227 Dortmund, Germany
    Proc Natl Acad Sci U S A 101:16431-6. 2004
  5. ncbi request reprint A mechanism for the potent inhibition of eukaryotic acetyl-coenzyme A carboxylase by soraphen A, a macrocyclic polyketide natural product
    Yang Shen
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Mol Cell 16:881-91. 2004
  6. pmc Acetyl-coenzyme A carboxylases: versatile targets for drug discovery
    Liang Tong
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    J Cell Biochem 99:1476-88. 2006
  7. ncbi request reprint Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery
    L Tong
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Cell Mol Life Sci 62:1784-803. 2005
  8. ncbi request reprint Carboxymethyl-phenylalanine as a replacement for phosphotyrosine in SH2 domain binding
    L Tong
    Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut 06877, USA
    J Biol Chem 273:20238-42. 1998
  9. ncbi request reprint Conserved mode of peptidomimetic inhibition and substrate recognition of human cytomegalovirus protease
    L Tong
    Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut 06877, USA
    Nat Struct Biol 5:819-26. 1998
  10. pmc Crystallization and preliminary crystallographic analysis of recombinant human P38 MAP kinase
    S Pav
    Department of Inflammatory Diseases, Boehringer Ingelheim Pharmaceuticals, Inc Ridgefield, Connecticut 06877, USA
    Protein Sci 6:242-5. 1997

Collaborators

Detail Information

Publications76

  1. ncbi request reprint How to take advantage of non-crystallographic symmetry in molecular replacement: 'locked' rotation and translation functions
    L Tong
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Acta Crystallogr D Biol Crystallogr 57:1383-9. 2001
    ..Moreover, the locked functions reduce the noise level in the calculation, owing to the averaging over the NCS elements, and increase the signals as all monomers of the assembly are taken into account at the same time...
  2. ncbi request reprint Pyrazole urea-based inhibitors of p38 MAP kinase: from lead compound to clinical candidate
    John Regan
    Department of Medicinal Chemistry, Research and Development Center, Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877, USA
    J Med Chem 45:2994-3008. 2002
    ..This modification affords significant improvements in binding, cellular, and in vivo potencies resulting in the selection of 45 (BIRB 796) as a clinical candidate for the treatment of inflammatory diseases...
  3. ncbi request reprint Crystal structures of substrate complexes of malic enzyme and insights into the catalytic mechanism
    Xiao Tao
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Structure 11:1141-50. 2003
    ..Tyr112-Lys183 functions as the general acid-base pair to catalyze the tautomerization of the enolpyruvate product from decarboxylation to pyruvate...
  4. pmc Structure and function of the phenazine biosynthetic protein PhzF from Pseudomonas fluorescens
    Wulf Blankenfeldt
    Max Planck Institute of Molecular Physiology, Otto Hahn Strasse 11, 44227 Dortmund, Germany
    Proc Natl Acad Sci U S A 101:16431-6. 2004
    ..Our proposed mechanism is supported by mass and NMR spectroscopy. The results are discussed in the context of related structures and protein sequences of unknown biochemical function...
  5. ncbi request reprint A mechanism for the potent inhibition of eukaryotic acetyl-coenzyme A carboxylase by soraphen A, a macrocyclic polyketide natural product
    Yang Shen
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Mol Cell 16:881-91. 2004
    ..Observations from native gel electrophoresis confirm this structural insight. The structural information provides a foundation for structure-based design of new inhibitors against these enzymes...
  6. pmc Acetyl-coenzyme A carboxylases: versatile targets for drug discovery
    Liang Tong
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    J Cell Biochem 99:1476-88. 2006
    ..This review summarizes these new progresses and also offers some prospects in terms of the future directions for the studies on these important enzymes...
  7. ncbi request reprint Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery
    L Tong
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Cell Mol Life Sci 62:1784-803. 2005
    ..The current intense research on these enzymes could lead to the development of novel therapies against metabolic syndrome and other diseases...
  8. ncbi request reprint Carboxymethyl-phenylalanine as a replacement for phosphotyrosine in SH2 domain binding
    L Tong
    Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut 06877, USA
    J Biol Chem 273:20238-42. 1998
    ....
  9. ncbi request reprint Conserved mode of peptidomimetic inhibition and substrate recognition of human cytomegalovirus protease
    L Tong
    Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut 06877, USA
    Nat Struct Biol 5:819-26. 1998
    ..HCMV protease therefore represents example of convergent evolution. In addition, large conformational differences relative to the structure of the free enzyme are observed, which may be important for inhibitor binding...
  10. pmc Crystallization and preliminary crystallographic analysis of recombinant human P38 MAP kinase
    S Pav
    Department of Inflammatory Diseases, Boehringer Ingelheim Pharmaceuticals, Inc Ridgefield, Connecticut 06877, USA
    Protein Sci 6:242-5. 1997
    ..The cell parameters for crystal form 1 are a = 65.2 A, b = 74.6 A and c = 78.1 A. Those for crystal form 2 are a = 58.3 A, b = 68.3 A and c = 87.9 A. Diffraction data to 2.0 A resolution have been collected on both forms...
  11. pmc Structural basis of inhibition of CDK-cyclin complexes by INK4 inhibitors
    P D Jeffrey
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Genes Dev 14:3115-25. 2000
    ..These observations support the model that INK4 binding weakens the cyclin's affinity for the CDK. This structure also provides insights into the specificity of the D-type cyclins for Cdk4/6...
  12. ncbi request reprint Investigating the role of histidine 157 in the catalytic activity of human cytomegalovirus protease
    R Khayat
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Biochemistry 40:6344-51. 2001
    ..Finally, structural comparisons revealed the presence of two conserved structural water molecules at the bottom of the S(1) pocket, suggesting a possible new direction for the design of HCMV protease inhibitors...
  13. ncbi request reprint A new serine-protease fold revealed by the crystal structure of human cytomegalovirus protease
    L Tong
    Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut 06877, USA
    Nature 383:272-5. 1996
    ..A dimer of the protease with an extensive interface is found in the crystal structure. This structure information will help in the design and optimization of inhibitors against herpesvirus proteases...
  14. ncbi request reprint Potent and competitive inhibition of malic enzymes by lanthanide ions
    Z Yang
    Department of Biological Sciences, Columbia University, New York, New York, 10027, USA
    Biochem Biophys Res Commun 274:440-4. 2000
    ....
  15. ncbi request reprint Structure of a closed form of human malic enzyme and implications for catalytic mechanism
    Z Yang
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nat Struct Biol 7:251-7. 2000
    ..Changes in tetramer organization of the enzyme are also observed in these complexes, which might be relevant for its cooperative behavior and allosteric control...
  16. ncbi request reprint Molecular mechanism for dimerization to regulate the catalytic activity of human cytomegalovirus protease
    R Batra
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nat Struct Biol 8:810-7. 2001
    ..Our studies suggest that appropriate dimer formation may be required to indirectly stabilize the protease oxyanion hole, revealing a novel mechanism for dimerization to regulate enzyme activity...
  17. ncbi request reprint Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a
    A A Russo
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nature 395:237-43. 1998
    ..Tumour-derived mutations in INK4a and Cdk4 map to interface contacts, solidifying the role of CDK binding and inhibition in the tumour suppressor activity of p16INK4a...
  18. ncbi request reprint Solution-state NMR investigations of triosephosphate isomerase active site loop motion: ligand release in relation to active site loop dynamics
    S Rozovsky
    Department of Chemistry, Columbia University, New York, NY 10027, USA
    J Mol Biol 310:271-80. 2001
    ..The rate of ligand release is less than 1000 s(-1) at 0 degrees C and more than 1000 s(-1) at 30 degrees C. Therefore, loop motion and product release are probably concerted and likely to represent a rate limiting step for chemistry...
  19. ncbi request reprint Structural basis for self-association and receptor recognition of human TRAF2
    Y C Park
    Department of Biochemistry, The Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, New York 10021, USA
    Nature 398:533-8. 1999
    ..The trimeric structure of the TRAF domain provides an avidity-based explanation for the dependence of TRAF recruitment on the oligomerization of the receptors by their trimeric extracellular ligands...
  20. ncbi request reprint Structural basis for signal transduction by the Toll/interleukin-1 receptor domains
    Y Xu
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nature 408:111-5. 2000
    ....
  21. ncbi request reprint Crystal structure of human mitochondrial NAD(P)+-dependent malic enzyme: a new class of oxidative decarboxylases
    Y Xu
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Structure 7:R877-89. 1999
    ..Moreover, this isoform is unique among malic enzymes in that it is a cooperative enzyme, and its activity is controlled allosterically...
  22. ncbi request reprint 2',6'-Dimethylphenoxyacetyl: a new achiral high affinity P(3)-P(2) ligand for peptidomimetic-based HIV protease inhibitors
    P L Beaulieu
    Boehringer Ingelheim Pharmaceuticals Inc, 175 Briar Ridge Road, Ridgefield, Connecticut 06877, USA
    J Med Chem 43:1094-108. 2000
    ....
  23. ncbi request reprint Binding site elucidation of hydantoin-based antagonists of LFA-1 using multidisciplinary technologies: evidence for the allosteric inhibition of a protein--protein interaction
    K Last-Barney
    Research and Development Center, Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877, USA
    J Am Chem Soc 123:5643-50. 2001
    ..The atomic details of the protein/antagonist interaction were accurately predicted by this model, as subsequently confirmed by the X-ray crystal structure of the complex...
  24. ncbi request reprint Viral proteases
    Liang Tong
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Chem Rev 102:4609-26. 2002
  25. ncbi request reprint COMO: a program for combined molecular replacement
    G Jogl
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Acta Crystallogr D Biol Crystallogr 57:1127-34. 2001
    ..A case is presented where the program automatically determined the orientation and position of five copies of a search model in a high-symmetry space group...
  26. ncbi request reprint A highly specific inhibitor of human p38 MAP kinase binds in the ATP pocket
    L Tong
    Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut 06877, USA
    Nat Struct Biol 4:311-6. 1997
    ..Other protein kinase inhibitors may achieve their specificity through a similar mechanism. The structure also reveals a possible second binding site for this inhibitor, with currently unknown function...
  27. pmc Molecular basis for the inhibition of the carboxyltransferase domain of acetyl-coenzyme-A carboxylase by haloxyfop and diclofop
    Hailong Zhang
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Proc Natl Acad Sci U S A 101:5910-5. 2004
    ..Two residues that affect herbicide sensitivity are located in this binding site, and mutation of these residues disrupts the structure of the domain. Other residues in the binding site are strictly conserved among the CT domains...
  28. ncbi request reprint Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase
    Hailong Zhang
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Science 299:2064-7. 2003
    ..Mutagenesis and kinetic studies reveal the functional roles of conserved residues here. The herbicides target the active site of CT, providing a lead for inhibitor development against human ACCs...
  29. ncbi request reprint The Myxococcus xanthus wbgB gene encodes a glycosyltransferase homologue required for lipopolysaccharide O-antigen biosynthesis
    Z Yang
    Department of Biological Sciences, Auburn University, AL 36849, USA
    Arch Microbiol 174:399-405. 2000
    ..xanthus cells. The pleiotrophic effects of wbgB mutations indicate the importance of LPS O-antigen biosynthesis for various cellular functions in M. xanthus...
  30. ncbi request reprint Crystal structure of human Taspase1, a crucial protease regulating the function of MLL
    Javed A Khan
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Structure 13:1443-52. 2005
    ..The structure unexpectedly showed the binding of a chloride ion in the active site, and our kinetic studies confirm that chlorides ions are inhibitors of this enzyme at physiologically relevant concentrations...
  31. ncbi request reprint Nicotinamide adenine dinucleotide metabolism as an attractive target for drug discovery
    Javed A Khan
    Columbia University, Department of Biological Sciences, New York, NY 10027, USA
    Expert Opin Ther Targets 11:695-705. 2007
    ..This review summarizes the existing knowledge on NAD(+) metabolic enzymes, with emphasis on their relevance for drug discovery...
  32. ncbi request reprint Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site
    Christopher Pargellis
    Department of Biology, Boehringer Ingelheim Pharmaceuticals, Research and Development Center, 900 Ridgebury Road, Ridgefield, Connecticut 06877, USA
    Nat Struct Biol 9:268-72. 2002
    ..One of the most potent compounds in this series, BIRB 796, has picomolar affinity for the kinase and low nanomolar inhibitory activity in cell culture...
  33. pmc Crystal structures of respiratory pathogen neuraminidases
    Yu Shan Hsiao
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Biochem Biophys Res Commun 380:467-71. 2009
    ..This work represents an important step in the development of drugs to prevent respiratory tract colonization by these two pathogens...
  34. pmc A different mechanism for the inhibition of the carboxyltransferase domain of acetyl-coenzyme A carboxylase by tepraloxydim
    Song Xiang
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Proc Natl Acad Sci U S A 106:20723-7. 2009
    ..Despite the chemical diversity between haloxyfop and tepraloxydim, the compounds do share two binding interactions to the enzyme, which may be important anchoring points for the development of ACC inhibitors...
  35. doi request reprint Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction
    Song Xiang
    Department of Biological Sciences, 212 Amsterdam Avenue, Columbia University, New York, New York 10027, USA
    Nat Struct Mol Biol 15:295-302. 2008
    ..There are dramatic differences in domain positions in the monomer and the organization of the tetramer between these enzymes and the PC from Rhizobium etli...
  36. ncbi request reprint Structural and functional evidence for Bacillus subtilis PaiA as a novel N1-spermidine/spermine acetyltransferase
    Farhad Forouhar
    Department of Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, New York 10027, USA
    J Biol Chem 280:40328-36. 2005
    ..In addition to preventing toxicity due to polyamine excess, this function may also serve to regulate expression of certain bacterial gene products such as those involved in sporulation...
  37. pmc Biochemical and functional studies on the regulation of the Saccharomyces cerevisiae AMPK homolog SNF1
    Gabriele A Amodeo
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Biochem Biophys Res Commun 397:197-201. 2010
    ..This suggests that residues 450-500 may be constitutively associated with Snf4, and the remaining segments of the RS, as well as the AID, may be involved in regulating SNF1 activity...
  38. pmc A symmetrical tetramer for S. aureus pyruvate carboxylase in complex with coenzyme A
    Linda P C Yu
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Structure 17:823-32. 2009
    ..Our structural information suggests that acetyl-CoA promotes a conformation for the dimer of the biotin carboxylase domain of PC that might be catalytically more competent...
  39. pmc Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase
    Christine S Huang
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nature 466:1001-5. 2010
    ....
  40. pmc The use of in situ proteolysis in the crystallization of murine CstF-77
    Yun Bai
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Acta Crystallogr Sect F Struct Biol Cryst Commun 63:135-8. 2007
    ..After an extensive search, it was found that 55% glucose can be used as a cryoprotectant while maintaining the diffraction quality of the crystals; most other commonly used cryoprotectants were detrimental to the diffraction quality...
  41. pmc Crystal structure of AGR_C_4470p from Agrobacterium tumefaciens
    Sergey M Vorobiev
    Department of Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, New York 10027, USA
    Protein Sci 16:535-8. 2007
    ..This is supported by the presence of two homologs of AGR_C_4470p in E. coli, in addition to the ChuS protein...
  42. ncbi request reprint Crystal structure of murine CstF-77: dimeric association and implications for polyadenylation of mRNA precursors
    Yun Bai
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Mol Cell 25:863-75. 2007
    ..The mode of dimerization and the relative arrangement of the HAT-N and HAT-C domains are unique to CstF-77. Our data support a role for CstF dimerization in pre-mRNA 3' end processing...
  43. pmc Structural evidence for direct interactions between the BRCT domains of human BRCA1 and a phospho-peptide from human ACC1
    Yang Shen
    Department of Biological Sciences, Columbia University, New York City, New York 10027, USA
    Biochemistry 47:5767-73. 2008
    ..Our studies establish a framework for understanding the regulation of lipid biosynthesis by BRCA1 through its inhibition of ACC1 activity, which could be a novel tumor suppressor function of BRCA1...
  44. ncbi request reprint Functional insights from structural genomics
    Farhad Forouhar
    Department of Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, NY 10027, USA
    J Struct Funct Genomics 8:37-44. 2007
    ..coli EutN), a proline racemase homolog with a disrupted active site (B. melitensis BME11586), an FMN-dependent enzyme (S. pneumoniae SP_1951), and a 12-stranded beta-barrel with a novel fold (V. parahaemolyticus VPA1032)...
  45. ncbi request reprint Structural and functional studies of the abundant tegument protein ORF52 from murine gammaherpesvirus 68
    Jordi Benach
    Department of Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, New York 10027, USA
    J Biol Chem 282:31534-41. 2007
    ..The results of the functional studies are fully consistent with the structural observations and indicate that the N-terminal alpha-helix is a crucial site of interaction for ORF52...
  46. pmc Molecular insights into substrate recognition and catalysis by tryptophan 2,3-dioxygenase
    Farhad Forouhar
    Department of Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, NY 10027, USA
    Proc Natl Acad Sci U S A 104:473-8. 2007
    ..The active site is completely devoid of water during catalysis, which is supported by our electrochemical studies showing significant stabilization of the enzyme upon substrate binding...
  47. ncbi request reprint Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with CP-640186
    Hailong Zhang
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Structure 12:1683-91. 2004
    ..The affinity of inhibitors for the CT domain has been assessed using kinetic and fluorescence anisotropy binding studies. The structural information identifies three regions for drug binding in the active site of CT...
  48. ncbi request reprint A novel NAD-binding protein revealed by the crystal structure of 2,3-diketo-L-gulonate reductase (YiaK)
    Farhad Forouhar
    Department of Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, NY 10027, USA
    J Biol Chem 279:13148-55. 2004
    ..The free enzyme conformation is incompatible with NAD binding. His(44) is likely the catalytic residue of the enzyme...
  49. ncbi request reprint Crystal structure of yeast acetyl-coenzyme A synthetase in complex with AMP
    Gerwald Jogl
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Biochemistry 43:1425-31. 2004
    ..A rotation of 140 degrees in the small domain is needed for the binding of CoA and the catalysis of the second step. In contrast to the monomeric bacterial enzyme, yeast ACS is a stable trimer...
  50. ncbi request reprint Structural and biochemical studies of the substrate selectivity of carnitine acetyltransferase
    Yu Shan Hsiao
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    J Biol Chem 279:31584-9. 2004
    ..8-A resolution. The F565A mutation has minor effects on the structure or the substrate preference of the enzyme...
  51. pmc Optimal alignment for enzymatic proton transfer: structure of the Michaelis complex of triosephosphate isomerase at 1.2-A resolution
    Gerwald Jogl
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Proc Natl Acad Sci U S A 100:50-5. 2003
    ....
  52. ncbi request reprint Aspartate dehydrogenase, a novel enzyme identified from structural and functional studies of TM1643
    Zhiru Yang
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    J Biol Chem 278:8804-8. 2003
    ..Therefore, our studies demonstrate that two different enzymes, an oxidase and a dehydrogenase, may have evolved to catalyze the first step of NAD biosynthesis in prokaryotes. TM1643 establishes a new class of amino acid dehydrogenases...
  53. ncbi request reprint An extensively associated dimer in the structure of the C713S mutant of the TIR domain of human TLR2
    Xiao Tao
    Department of Biological Sciences, Columbia University, 10027, New York, NY, USA
    Biochem Biophys Res Commun 299:216-21. 2002
    ..Moreover, the structure shows that the BB loop can adopt different conformations, which are required for the formation of this dimer. This asymmetric dimer might represent the TLR2:TLRx heterodimer in the function of this receptor...
  54. ncbi request reprint Crystal structures of MTH1187 and its yeast ortholog YBL001c
    Xiao Tao
    Department of Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, New York 10027, USA
    Proteins 52:478-80. 2003
  55. pmc Structural studies of the pigeon cytosolic NADP(+)-dependent malic enzyme
    Zhiru Yang
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Protein Sci 11:332-41. 2002
    ..Our structural studies also revealed differences in the organization of the tetramer between the pigeon and the human enzymes, although the pigeon enzyme still obeys 222 symmetry...
  56. ncbi request reprint Characterization of the monomer-dimer equilibrium of human cytomegalovirus protease by kinetic methods
    Reza Khayat
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Biochemistry 43:316-22. 2004
    ..5 M Na2SO4), respectively. Detailed kinetic analysis also showed that, in addition to the 260-fold stabilization of the dimer, the anti-chaotropic agents produced a 7-fold enhancement in the catalytic activity of the dimer...
  57. ncbi request reprint Crystal structure of human nicotinamide riboside kinase
    Javed A Khan
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Structure 15:1005-13. 2007
    ..Mutation of residues in the active site can abolish the catalytic activity of the enzyme, confirming the structural observations...
  58. ncbi request reprint Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses
    Cuifeng Yin
    Center for Advanced Biotechnology and Medicine, Northeast Structural Genomics Consortium, Department of Molecular Biology and Biochemistry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA
    J Biol Chem 282:20584-92. 2007
    ..This pocket provides a target on the surface of the NS1 protein that is potentially suitable for the development of antiviral drugs targeting both influenza A and B viruses...
  59. ncbi request reprint Crystal structure of carnitine acetyltransferase and implications for the catalytic mechanism and fatty acid transport
    Gerwald Jogl
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Cell 112:113-22. 2003
    ..Specifically, our structural information suggests that the substrate carnitine may assist the catalysis by stabilizing the oxyanion in the reaction intermediate...
  60. ncbi request reprint How to get all "A"s in polyadenylation
    Corey R Mandel
    Structure 15:1024-6. 2007
    ....
  61. pmc Molecular insights into the biosynthesis of the F420 coenzyme
    Farhad Forouhar
    Department of Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, New York 10027, USA
    J Biol Chem 283:11832-40. 2008
    ..Large structural differences in the active site region of the non-F(420)-producing CofD homologs suggest that they catalyze a different biochemical reaction...
  62. pmc Crystal structure of the BEACH domain reveals an unusual fold and extensive association with a novel PH domain
    Gerwald Jogl
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    EMBO J 21:4785-95. 2002
    ..Functional studies in intact cells demonstrate the requirement of both the PH and the BEACH domains for activity. A prominent groove at the interface between the two domains may be used to recruit their binding partners...
  63. ncbi request reprint Crystal structure of human DJ-1, a protein associated with early onset Parkinson's disease
    Xiao Tao
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    J Biol Chem 278:31372-9. 2003
    ..The DJ-1 proteins may function only as dimers. The Lys to Arg mutation at residue 130, the site of sumoylation of DJ-1, has minimal impact on the structure of the protein...
  64. pmc Crystal structure of the MAP kinase binding domain and the catalytic domain of human MKP5
    Xiao Tao
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Protein Sci 16:880-6. 2007
    ..The CD of MKP5 is observed in an active conformation, and two loops in the active site have backbone shifts of up to 5 A relative to the inactive CDs from other MKPs...
  65. ncbi request reprint Crystal structure of mouse carnitine octanoyltransferase and molecular determinants of substrate selectivity
    Gerwald Jogl
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    J Biol Chem 280:738-44. 2005
    ..The side chains of Cys-323 and Met-335 at the bottom of this pocket assume dual conformations in the substrate complex, and mutagenesis studies suggest that the Met-335 residue is important for catalysis...
  66. ncbi request reprint Crystal structure of the PH-BEACH domains of human LRBA/BGL
    Damara Gebauer
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Biochemistry 43:14873-80. 2004
    ..The structure suggests intimate association between the PH and the BEACH domains, and surface plasmon resonance studies confirm that the two domains of the protein FAN have high affinity for each other, with a K(d) of 120 nM...
  67. ncbi request reprint Structural and biochemical studies of inhibitor binding to human cytomegalovirus protease
    Reza Khayat
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Biochemistry 42:885-91. 2003
    ..Favorable and stereospecific interactions have been established in the S(1)' pocket for one of these inhibitors...
  68. ncbi request reprint Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+ channels
    Yu hang Chen
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nature 429:675-80. 2004
    ..The presence of multiple protein-interacting modules in the beta-subunit opens a new dimension to its function as a multi-functional protein...
  69. ncbi request reprint Engineering d-amino acid containing novel protease inhibitors using catalytic site architecture
    Subhash C Annedi
    Molecular Design and Information Technology Center, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada ON M5S 2S2
    Bioorg Med Chem 14:214-36. 2006
    ..More potent and specific inhibitors could be designed with structure optimization as this strategy is completely general and can be used to design inhibitors against any serine or cysteine protease...
  70. ncbi request reprint Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents
    Javed A Khan
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nat Struct Mol Biol 13:582-8. 2006
    ..Contrary to current knowledge, the structures show that FK866 should compete directly with the nicotinamide substrate. Our structural and biochemical studies provide a starting point for the development of new anticancer agents...
  71. pmc Crystal structures of murine carnitine acetyltransferase in ternary complexes with its substrates
    Yu Shan Hsiao
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    J Biol Chem 281:28480-7. 2006
    ..The structural information provides significant new insights into the catalytic mechanism of CrAT and possibly carnitine acyltransferases in general...
  72. ncbi request reprint Metal-Induced reversible structural interconversion of human mitochondrial NAD(P)+-dependent malic enzyme
    Chu Wei Kuo
    Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan
    Proteins 54:404-11. 2004
    ..Excess Mn2+ could replace Lu3+ in the metal binding site and convert the inactive form back into the open form. This reversible process was slow in both directions because of the same but opposite structural change involved...
  73. ncbi request reprint Crystal structure of 1-deoxy-D-xylulose 5-phosphate synthase, a crucial enzyme for isoprenoids biosynthesis
    Song Xiang
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    J Biol Chem 282:2676-82. 2007
    ..The structures identify residues that may have important roles in catalysis, which have been confirmed by our mutagenesis studies...
  74. ncbi request reprint Functional and structural basis of carnitine palmitoyltransferase 1A deficiency
    Stephanie Gobin
    Departement d Endocrinologie, Institut Cochin, INSERM U567, CNRS Unité Mixte de Recherche 8104, Universite Rene Descartes, 24 rue du Faubourg Saint Jacques, 75014 Paris, France
    J Biol Chem 278:50428-34. 2003
    ..This study provides novel insights into the functionality of CPT1A that may contribute to the design of drugs for the treatment of lipid disorders...
  75. ncbi request reprint Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7)
    Robert Hering
    Department of Medical Genetics, University of Tubingen, Tubingen, Germany
    Hum Mutat 24:321-9. 2004
    ....
  76. ncbi request reprint Structure of the Bateman2 domain of yeast Snf4: dimeric association and relevance for AMP binding
    Michael J Rudolph
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Structure 15:65-74. 2007
    ..There is a prominent pocket at the center of this dimer, and most of the disease-causing mutations are located in or near this pocket...