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Genomes and Genes | T P BegleySummaryAffiliation: Cornell University Country: USA Publications
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The structural basis for the remarkable catalytic proficiency of orotidine 5'-monophosphate decarboxylaseT P Begley
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
Curr Opin Struct Biol 10:711-8. 2000....- Cofactor biosynthesis: an organic chemist's treasure troveTadhg P Begley
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
Nat Prod Rep 23:15-25. 2006 - Enzymatic reactions involving novel mechanisms of carbanion stabilizationTadhg P Begley
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, NY14853, USA
Curr Opin Chem Biol 8:508-15. 2004.... - The enzymology of sulfur activation during thiamin and biotin biosynthesisT 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... - Thiamin biosynthesis in prokaryotesT 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... 
Cofactor biosynthesis--still yielding fascinating new biological chemistryTadhg 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...- Chemical biology: an educational challenge for chemistry departmentsTadhg 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... - The mechanism of action of bacimethrin, a naturally occurring thiamin antimetaboliteJ 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... - Structural characterization of the enzyme-substrate, enzyme-intermediate, and enzyme-product complexes of thiamin phosphate synthaseD H Peapus
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
Biochemistry 40:10103-14. 2001.... - Efficient sequence analysis of the six gene products (7-74 kDa) from the Escherichia coli thiamin biosynthetic operon by tandem high-resolution mass spectrometryN 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... - Thiamin biosynthesis in Escherichia coli. Identification of ThiS thiocarboxylate as the immediate sulfur donor in the thiazole formationS 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... - 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 complexJ 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... - Overexpression of recombinant proteins with a C-terminal thiocarboxylate: implications for protein semisynthesis and thiamin biosynthesisC 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... - Crystal structure of thiamin phosphate synthase from Bacillus subtilis at 1.25 A resolutionH J Chiu
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
Biochemistry 38:6460-70. 1999.... - Solution structure of ThiS and implications for the evolutionary roots of ubiquitinC 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... - Phosphopantothenoylcysteine synthetase from Escherichia coli. Identification and characterization of the last unidentified coenzyme A biosynthetic enzyme in bacteriaE 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... - The crystal structure and mechanism of orotidine 5'-monophosphate decarboxylaseT 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... - Crystal structure of 4-methyl-5-beta-hydroxyethylthiazole kinase from Bacillus subtilis at 1.5 A resolutionN Campobasso
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
Biochemistry 39:7868-77. 2000.... - Structural genes for thiamine biosynthetic enzymes (thiCEFGH) in Escherichia coli K-12P 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... - Characterization of the Bacillus subtilis thiC operon involved in thiamine biosynthesisY 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... - Identification of the Escherichia coli nicotinic acid mononucleotide adenylyltransferase geneR 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... - Two-dimensional mass spectrometry of biomolecules at the subfemtomole levelF 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... - The biosynthesis of coenzyme A in bacteriaT 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... - Mechanistic studies on thiamin phosphate synthase: evidence for a dissociative mechanismJ J Reddick
Department of Chemistry and Chemical Biology, 120 Baker Laboratory, Cornell University, Ithaca, New York 14853, USA
Biochemistry 40:10095-102. 2001.... - The biosynthesis of nicotinamide adenine dinucleotides in bacteriaT 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... - Top-down MS, a powerful complement to the high capabilities of proteolysis proteomicsFred W McLafferty
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, NY 14853, USA
FEBS J 274:6256-68. 2007.... - Mutagenesis studies on TenA: a thiamin salvage enzyme from Bacillus subtilisAmy 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... - Gene identification and structural characterization of the pyridoxal 5'-phosphate degradative protein 3-hydroxy-2-methylpyridine-4,5-dicarboxylate decarboxylase from mesorhizobium loti MAFF303099Tathagata 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... - Structure of oxalate decarboxylase from Bacillus subtilis at 1.75 A resolutionRuchi 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... - Trapping of a chromophoric intermediate in the Pdx1-catalyzed biosynthesis of pyridoxal 5'-phosphateJeremiah W Hanes
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
Angew Chem Int Ed Engl 47:2102-5. 2008 - Structural studies on 3-hydroxyanthranilate-3,4-dioxygenase: the catalytic mechanism of a complex oxidation involved in NAD biosynthesisYang 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... - Comparison of femtosecond laser and continuous wave UV sources for protein-nucleic acid crosslinkingChristopher 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... - Crystal structure of mammalian cysteine dioxygenase. A novel mononuclear iron center for cysteine thiol oxidationChad R Simmons
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853 8001, USA
J Biol Chem 281:18723-33. 2006.... - Stereochemical studies on phosphopantothenoylcysteine decarboxylase from Escherichia coliErick 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... - Thiamin biosynthesis in Bacillus subtilis: structure of the thiazole synthase/sulfur carrier protein complexEthan 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... - Structure of the PLP degradative enzyme 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase from Mesorhizobium loti MAFF303099 and its mechanistic implicationsKathryn 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... - Crystal structure of 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase from Salmonella typhimurium at 2.3 A resolutionGong 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... - Structure of human phosphopantothenoylcysteine synthetase at 2.3 A resolutionNarayanan 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... 
Structural studies of thiamin monophosphate kinase in complex with substrates and productsKathryn 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...- Structure determination and characterization of the vitamin B6 degradative enzyme (E)-2-(acetamidomethylene)succinate hydrolaseKathryn 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... - DNA-protein cross-linking: model systems for pyrimidine-aromatic amino acid cross-linkingGuangxing 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... - Biosynthesis of thiamin thiazole: determination of the regiochemistry of the S/O acyl shift by using 1,4-dideoxy-D-xylulose-5-phosphateAbhishek Chatterjee
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
Angew Chem Int Ed Engl 45:3507-10. 2006 - Biosynthesis of the thiamin thiazole in Bacillus subtilis: identification of the product of the thiazole synthase-catalyzed reactionAmrita 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... - Structural insights into the mechanism of the PLP synthase holoenzyme from Thermotoga maritimaFairuz 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... - Crystal structure and mechanism of tryptophan 2,3-dioxygenase, a heme enzyme involved in tryptophan catabolism and in quinolinate biosynthesisYang 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... - Structural similarities between thiamin-binding protein and thiaminase-I suggest a common ancestorErika 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... - Thiamin phosphate synthase: the rate of pyrimidine carbocation formationJeremiah W Hanes
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
J Am Chem Soc 129:4860-1. 2007 - Biosynthesis of the thiamin-thiazole in eukaryotes: identification of a thiazole tautomer intermediateAbhishek 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... - An assay for thiaminase I in complex biological samplesJeremiah 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... - A new thiamin salvage pathwayAmy 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... - 13C NMR snapshots of the complex reaction coordinate of pyridoxal phosphate synthaseJeremiah 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... - Catalysis of a flavoenzyme-mediated amide hydrolysisTathagata 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... - Thiamin biosynthesis in eukaryotes: characterization of the enzyme-bound product of thiazole synthase from Saccharomyces cerevisiae and its implications in thiazole biosynthesisAbhishek 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... - Structure of the Escherichia coli ThiS-ThiF complex, a key component of the sulfur transfer system in thiamin biosynthesisChristopher 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... - The biosynthesis of the thiazole phosphate moiety of thiamin (vitamin B1): the early steps catalyzed by thiazole synthasePieter 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... - Structural biology of enzymes of the thiamin biosynthesis pathwayEthan 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... - Structural characterization of the regulatory proteins TenA and TenI from Bacillus subtilis and identification of TenA as a thiaminase IIAngela 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... - The biosynthesis of the thiazole phosphate moiety of thiamin: the sulfur transfer mediated by the sulfur carrier protein ThiSPieter 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... - Three-dimensional structure of YaaE from Bacillus subtilis, a glutaminase implicated in pyridoxal-5'-phosphate biosynthesisJacob 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... - Oxidative cascades: a facile biosynthetic strategy for the assembly of complex moleculesPieter 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... - Top down characterization of secreted proteins from Mycobacterium tuberculosis by electron capture dissociation mass spectrometryYing 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... - Structural and mechanistic studies on ThiO, a glycine oxidase essential for thiamin biosynthesis in Bacillus subtilisEthan 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... - Top down characterization of larger proteins (45 kDa) by electron capture dissociation mass spectrometryYing 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... - Thi20, a remarkable enzyme from Saccharomyces cerevisiae with dual thiamin biosynthetic and degradation activitiesAmy 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... - Reconstitution of a new cysteine biosynthetic pathway in Mycobacterium tuberculosisKristin 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... - Mechanistic studies on phosphopantothenoylcysteine decarboxylase: trapping of an enethiolate intermediate with a mechanism-based inactivating agentErick Strauss
Department of Chemistry, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa
Biochemistry 43:15520-33. 2004.... - Identification of the two missing bacterial genes involved in thiamine salvage: thiamine pyrophosphokinase and thiamine kinaseJonathan 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... - An efficient enzymatic synthesis of thiamin pyrophosphateJonathan 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... - A genetic screen for the identification of thiamin metabolic genesBrian 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... - The selectivity for cysteine over serine in coenzyme A biosynthesisErick Strauss
Department of Chemistry, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa
Chembiochem 6:284-6. 2005 - Biosynthesis of the thiamin pyrimidine: the reconstitution of a remarkable rearrangement reactionBrian 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... - Simultaneous kinetic characterization of multiple protein forms by top down mass spectrometryHuili 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... - The antibiotic activity of N-pentylpantothenamide results from its conversion to ethyldethia-coenzyme a, a coenzyme a antimetaboliteErick 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... - Functional copper at the acetyl-CoA synthase active siteJavier 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... - O-phospho-L-serine and the thiocarboxylated sulfur carrier protein CysO-COSH are substrates for CysM, a cysteine synthase from Mycobacterium tuberculosisSeán 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... - Vitamin B1 de novo synthesis in the human malaria parasite Plasmodium falciparum depends on external provision of 4-amino-5-hydroxymethyl-2-methylpyrimidineCarsten 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... - The mechanism of inactivation of 3-hydroxyanthranilate-3,4-dioxygenase by 4-chloro-3-hydroxyanthranilateKeri 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... - 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.... - Reconstitution and biochemical characterization of a new pyridoxal-5'-phosphate biosynthetic pathwayKristin 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... - Mechanistic studies on pyridoxal phosphate synthase: the reaction pathway leading to a chromophoric intermediateJeremiah 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... - Structural insights into the function of the thiamin biosynthetic enzyme Thi4 from Saccharomyces cerevisiaeChristopher 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... - NAD biosynthesis: identification of the tryptophan to quinolinate pathway in bacteriaOleg 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... - Characterization of two kinases involved in thiamine pyrophosphate and pyridoxal phosphate biosynthesis in Bacillus subtilis: 4-amino-5-hydroxymethyl-2methylpyrimidine kinase and pyridoxal kinaseJoo-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... - Biosynthesis of the thioquinolobactin siderophore: an interesting variation on sulfur transferAmy 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... - Biochemistry: molecular cannibalismSteven E Ealick
Nature 446:387-8. 2007 - Biosynthesis of thiamin thiazole in eukaryotes: conversion of NAD to an advanced intermediateAbhishek 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 Grants
- CHEMISTRY OF BIOLOGICAL SYSTEMSTadhg 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. ..