Research Topics
| JOHN GERLTSummaryAffiliation: University of Illinois Country: USA Publications
Research Grants
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Detail Information
Publications
The Enzyme Function InitiativeJohn A Gerlt
Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
Biochemistry 50:9950-62. 2011....- Divergent evolution in enolase superfamily: strategies for assigning functionsJohn A Gerlt
Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
J Biol Chem 287:29-34. 2012..We describe strategies for assigning functions to members of the enolase superfamily that should be applicable to other superfamilies... 
A gold standard set of mechanistically diverse enzyme superfamiliesShoshana D Brown
Department of Biopharmaceutical Sciences, University of California, 1700 4th Street, San Francisco, San Francisco, CA 94143-2550, USA
Genome Biol 7:R8. 2006..The gold standard set represents four fold classes and differing clustering difficulties, and includes five superfamilies, 91 families, 4,887 sequences and 282 structures...
A Protein Structure (or Function ?) InitiativeJohn A Gerlt
Department of Biochemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA
Structure 15:1353-6. 2007- Enzyme (re)design: lessons from natural evolution and computationJohn A Gerlt
Departments of Biochemistry and Chemistry, University of Illinois, Urbana, 61801, United States
Curr Opin Chem Biol 13:10-8. 2009..This review summarizes recent progress in evolution-based and computation-based (re)design... - Divergent evolution in the enolase superfamily: the interplay of mechanism and specificityJohn A Gerlt
Departments of Biochemistry and Chemistry, University of Illinois, Urbana, IL 61801, USA
Arch Biochem Biophys 433:59-70. 2005..In this minireview, our current understanding of structure/function relationships in the divergent members of the superfamily is reviewed, and the use of this knowledge for our future studies is proposed... - Divergent evolution of enzymatic function: mechanistically diverse superfamilies and functionally distinct suprafamiliesJ A Gerlt
Departments of Biochemistry and Chemistry, University of Illinois, Urbana, Illinois 61801, USA
Annu Rev Biochem 70:209-46. 2001.... - Can sequence determine function?J A Gerlt
Departments of Biochemistry and Chemistry, University of Illinois, Urbana, IL 61801, USA
Genome Biol 1:REVIEWS0005. 2000.... - Mechanistically diverse enzyme superfamilies: the importance of chemistry in the evolution of catalysisJ A Gerlt
Department of Biochemistry, University of Illinois at Urbana Champaign 61801, USA
Curr Opin Chem Biol 2:607-12. 1998..Recent work supports a strategy in which a partial reaction, catalyzed by a progenitor, is retained, and the active-site architecture is modified to allow the intermediate generated to be directed to different products... - Understanding enzymic catalysis: the importance of short, strong hydrogen bondsJ A Gerlt
Department of Biochemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL 61801, USA
Chem Biol 4:259-67. 1997..Here, we defend this proposal and provide evidence for likely changes of hydrogen bond strengths during enzymic catalysis... - Evolutionary potential of (beta/alpha)8-barrels: in vitro enhancement of a "new" reaction in the enolase superfamilyJacob E Vick
Department of Biochemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
Biochemistry 44:11722-9. 2005..These observations support our hypothesis that evolution of "new" functions in the enolase superfamily can occur simply by changes in specificity-determining residues... - Evolutionary potential of (beta/alpha)8-barrels: functional promiscuity produced by single substitutions in the enolase superfamilyDawn M Z Schmidt
Departments of Biochemistry and Chemistry, 419 Roger Adams Laboratory, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
Biochemistry 42:8387-93. 2003.... - Evolution of enzymatic activity in the enolase superfamily: structural and mutagenic studies of the mechanism of the reaction catalyzed by o-succinylbenzoate synthase from Escherichia coliVadim A Klenchin
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53705, USA
Biochemistry 42:14427-33. 2003..The epsilon-ammonium group of Lys 235 forms a cation-pi interaction with the cyclohexadienyl moiety of SHCHC, suggesting that Lys 235 also stabilizes the enediolate anion intermediate in the syn dehydration via a similar interaction... - Evolutionary potential of (beta/alpha)8-barrels: stepwise evolution of a "new" reaction in the enolase superfamilyJacob E Vick
Department of Biochemistry, University of Illinois at Urbana Champaign, 600 S Mathews Avenue, Urbana, Illinois 61801, USA
Biochemistry 46:14589-97. 2007.... - Evolution of function in the crotonase superfamily: (3S)-methylglutaconyl-CoA hydratase from Pseudomonas putidaBrian J Wong
Departments of Biochemistry and Chemistry, University of Illinois, Urbana, Illinois 61801, USA
Biochemistry 43:4646-54. 2004.... - Evolution of enzymatic activity in the enolase superfamily: functional studies of the promiscuous o-succinylbenzoate synthase from AmycolatopsisErika A Taylor Ringia
Departments of Biochemistry and Chemistry, University of Illinois, Urbana, IL 61801, USA
Biochemistry 43:224-9. 2004.... - Evolution of enzymatic activities in the orotidine 5'-monophosphate decarboxylase suprafamily: structural basis for catalytic promiscuity in wild-type and designed mutants of 3-keto-L-gulonate 6-phosphate decarboxylaseEric L Wise
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
Biochemistry 44:1816-23. 2005.... - Prediction and assignment of function for a divergent N-succinyl amino acid racemaseLing Song
Department of Biochemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
Nat Chem Biol 3:486-91. 2007..These studies establish that ligand docking to a homology model can facilitate functional assignment of unknown proteins by restricting the identities of the possible substrates that must be experimentally tested... - Obituary: Frank H. Westheimer (1912-2007)John A Gerlt
John A. Gerlt is in the Departments of Biochemistry and Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801
Nature 447:543. 2007 - Evolution of enzymatic activities in the enolase superfamily: D-tartrate dehydratase from Bradyrhizobium japonicumWen Shan Yew
Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
Biochemistry 45:14598-608. 2006.... - Evolution of enzymatic activities in the enolase superfamily: L-fuconate dehydratase from Xanthomonas campestrisWen Shan Yew
Department of Biochemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
Biochemistry 45:14582-97. 2006..The functional promiscuity discovered for FucD highlights possible structural mechanisms for evolution of function in the enolase superfamily... - Evolution of enzymatic activities in the enolase superfamily: structure of a substrate-liganded complex of the L-Ala-D/L-Glu epimerase from Bacillus subtilisVadim A Klenchin
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
Biochemistry 43:10370-8. 2004..M., Hubbard, B. K., and Gerlt, J. A. (2001) Biochemistry 40, 15707-15715]. These studies provide important new information about the structural bases for substrate specificity in the enolase superfamily... - Evolution of enzymatic activities in the enolase superfamily: L-rhamnonate dehydrataseJohn F Rakus
Department of Biochemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
Biochemistry 47:9944-54. 2008.... - Conformational changes in orotidine 5'-monophosphate decarboxylase: "remote" residues that stabilize the active conformationB McKay Wood
Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
Biochemistry 49:3514-6. 2010..The intrinsic binding energies of the 5'-phosphate group of orotidine 5'-monophosphate for the mutant enzymes are similar to that for the wild type, supporting this conclusion... - Evolution of enzymatic activities in the enolase superfamily: L-talarate/galactarate dehydratase from Salmonella typhimurium LT2Wen Shan Yew
Departments of Biochemistry and Chemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
Biochemistry 46:9564-77. 2007..The promiscuous catalytic activities discovered for STM3697 highlight the evolutionary potential of a "conserved" active site architecture... - Evolution of function in (beta/alpha)8-barrel enzymesJohn A Gerlt
Department of Biochemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
Curr Opin Chem Biol 7:252-64. 2003..Recent work has examined natural, designed, and directed evolution of function in several superfamilies of (beta/alpha)(8)-barrel containing enzymes... - Evolution of enzymatic activity in the enolase superfamily: structural studies of the promiscuous o-succinylbenzoate synthase from AmycolatopsisJames B Thoden
Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA
Biochemistry 43:5716-27. 2004..Accommodation of the components of the N-acyl linkage appears to be the reason that this enzyme is capable of a racemization reaction on these substrates, whereas the orthologous OSBS from Escherichia coli lacks this functionality... - Evolution of enzymatic activities in the orotidine 5'-monophosphate decarboxylase suprafamily: mechanistic evidence for a proton relay system in the active site of 3-keto-L-gulonate 6-phosphate decarboxylaseWen Shan Yew
Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
Biochemistry 43:6427-37. 2004..This study further highlights the opportunistic nature of divergent evolution in conscripting the active site of a progenitor to catalyze a mechanistically distinct reaction... - Evolution of enzymatic activities in the orotidine 5'-monophosphate decarboxylase suprafamily: crystallographic evidence for a proton relay system in the active site of 3-keto-L-gulonate 6-phosphate decarboxylaseEric L Wise
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
Biochemistry 43:6438-46. 2004..These studies further underscore the wide variation in the reaction mechanisms in the OMPDC suprafamily... - Evolution of enzymatic activities in the enolase superfamily: stereochemically distinct mechanisms in two families of cis,cis-muconate lactonizing enzymesAyano Sakai
Center for Biophysics and Computational Biology, University of Illinois, Urbana, Illinois 61801, USA
Biochemistry 48:1445-53. 2009.... - Mechanism of the orotidine 5'-monophosphate decarboxylase-catalyzed reaction: effect of solvent viscosity on kinetic constantsB McKay Wood
Department of Biochemistry, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, USA
Biochemistry 48:5510-7. 2009..e., substrate binding and product dissociation mask the kinetic effects of stabilization of the intermediate by the substituent... - D-Ribulose 5-phosphate 3-epimerase: functional and structural relationships to members of the ribulose-phosphate binding (beta/alpha)8-barrel superfamilyJulie Akana
Department of Biochemistry, University of Illinois at Urbana Champaign, 600 S Mathews Avenue, Urbana, Illinois 61801, USA
Biochemistry 45:2493-503. 2006..Instead, this "superfamily" may result from assembly from smaller modules, including the conserved phosphate binding motif associated with the C-terminal (beta/alpha)(2)-quarter barrel... - Mechanism of the orotidine 5'-monophosphate decarboxylase-catalyzed reaction: evidence for substrate destabilizationKui K Chan
Department of Biochemistry, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, USA
Biochemistry 48:5518-31. 2009..We propose that the differential effects of substitutions for Asp 70 of MtOMPDC on decarboxylation and exchange provide additional evidence for a carbanionic intermediate as well as the involvement of Asp 70 in substrate destabilization... - Structural basis for substrate specificity in phosphate binding (beta/alpha)8-barrels: D-allulose 6-phosphate 3-epimerase from Escherichia coli K-12Kui K Chan
Departments of Biochemistry and Chemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
Biochemistry 47:9608-17. 2008.... - Computation-facilitated assignment of the function in the enolase superfamily: a regiochemically distinct galactarate dehydratase from Oceanobacillus iheyensis John F Rakus
Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
Biochemistry 48:11546-58. 2009.... - Evolution of enzymatic activities in the orotidine 5'-monophosphate decarboxylase suprafamily: enhancing the promiscuous D-arabino-hex-3-ulose 6-phosphate synthase reaction catalyzed by 3-keto-L-gulonate 6-phosphate decarboxylaseWen Shan Yew
Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
Biochemistry 44:1807-15. 2005..Thus, the (beta/alpha)(8)-barrel fold shared by members of the OMPDC suprafamily appears well-suited for the evolution of new functions... - Homologous (beta/alpha)8-barrel enzymes that catalyze unrelated reactions: orotidine 5'-monophosphate decarboxylase and 3-keto-L-gulonate 6-phosphate decarboxylaseEric Wise
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
Biochemistry 41:3861-9. 2002..Accordingly, sequence or structure homology alone cannot be used to infer the functions of new proteins discovered in genome projects... - Evolution of enzymatic activities in the enolase superfamily: D-Mannonate dehydratase from Novosphingobium aromaticivoransJohn F Rakus
Department of Biochemistry, University of Illinois at Urbana Champaign, 600 S Mathews Avenue, Urbana, Illinois 61801, USA
Biochemistry 46:12896-908. 2007.... - Chemical and enzymatic synthesis of fluorinated-dehydroalanine-containing peptidesHao Zhou
Department of Chemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA
Chembiochem 4:1206-15. 2003..Mechanistic investigations showed that fluoride elimination occurred faster than epimerization and at a rate close to that of epimerization of Ala-Ala... - Structural evidence for a 1,2-enediolate intermediate in the reaction catalyzed by 3-keto-L-gulonate 6-phosphate decarboxylase, a member of the orotidine 5'-monophosphate decarboxylase suprafamilyEric L Wise
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
Biochemistry 42:12133-42. 2003..This study further demonstrates that multiple unrelated enzyme functions can evolve from a single active site architecture without regard for substrate binding affinity or mechanism... - Mechanistic diversity in the RuBisCO superfamily: the "enolase" in the methionine salvage pathway in Geobacillus kaustophilusHeidi J Imker
Departments of Biochemistry and Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
Biochemistry 46:4077-89. 2007..e., coordination to an essential Mg2+, but the proton abstraction is catalyzed by a different general base... - Divergent function in the crotonase superfamily: an anhydride intermediate in the reaction catalyzed by 3-hydroxyisobutyryl-CoA hydrolaseBrian J Wong
Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
J Am Chem Soc 125:12076-7. 2003..Thus, we conclude that the conserved oxyanion hole in this superfamily can be used to stabilize a variety of anionic intermediates... - Evolution of enzymatic activities in the enolase superfamily: N-succinylamino acid racemase and a new pathway for the irreversible conversion of D- to L-amino acidsAyano Sakai
Center for Biophysics and Computational Biology and Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
Biochemistry 45:4455-62. 2006..kaustophilus does not encode an OSBS, raising the possibility that the NSAR is a bifunctional enzyme rather than an accidentally promiscuous enzyme... - How to find "missing" genesJohn A Gerlt
Department of Biochemistry, University of Illinois, 415 Roger Adams Laboratory, 600 S Mathews Avenue, Urbana, IL 61801, USA
Chem Biol 10:1141-2. 2003..Osterman and Begley break down this barrier by demonstrating that comparative analyses of microbial genomes is a powerful strategy for identifying pathway components... - Evolution of function in the crotonase superfamily: the stereochemical course of the reaction catalyzed by 2-ketocyclohexanecarboxyl-CoA hydrolaseEllen D Eberhard
Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
J Am Chem Soc 126:7188-9. 2004.... - Utilization of L-ascorbate by Escherichia coli K-12: assignments of functions to products of the yjf-sga and yia-sgb operonsWen Shan Yew
Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
J Bacteriol 184:302-6. 2002.... - Evolution of enzyme superfamiliesMargaret E Glasner
Department of Biopharmaceutical Sciences, University of California, San Francisco, CA 94143, USA
Curr Opin Chem Biol 10:492-7. 2006..Understanding how enzyme superfamilies evolve is vital for accurate genome annotation, predicting protein functions, and protein engineering... - Mechanisms of protein evolution and their application to protein engineeringMargaret E Glasner
Department of Biopharmaceutical Sciences, University of California San Francisco, San Francisco, CA 94143, USA
Adv Enzymol Relat Areas Mol Biol 75:193-239, xii-xiii. 2007..Future research will determine if application of these principles will lead to a protein engineering methodology governed by predictable rules for designing efficient, novel catalysts... - Dissecting the total transition state stabilization provided by amino acid side chains at orotidine 5'-monophosphate decarboxylase: a two-part substrate approachShonoi A Barnett
Department of Chemistry, University at Buffalo, SUNY, Buffalo, New York 14260 3000, USA
Biochemistry 47:7785-7. 2008.... - Formation and stability of a vinyl carbanion at the active site of orotidine 5'-monophosphate decarboxylase: pKa of the C-6 proton of enzyme-bound UMPTina L Amyes
Department of Chemistry, University at Buffalo, Buffalo, New York 14260, USA
J Am Chem Soc 130:1574-5. 2008 - Evolution of structure and function in the o-succinylbenzoate synthase/N-acylamino acid racemase family of the enolase superfamilyMargaret E Glasner
Department of Biopharmaceutical Sciences, University of California, San Francisco, CA 94143, USA
J Mol Biol 360:228-50. 2006..Finally, a combination of evolutionary, structural, and sequence analyses identified characteristics that might prime proteins, such as Amycolatopsis OSBS/NAAAR, for the evolution of new activities... - Structure of D-ribulose 5-phosphate 3-epimerase from Synechocystis to 1.6 A resolutionEric L Wise
Deparment of Biochemistry, University of Wisconsin, Madison, WI 53706, USA
Acta Crystallogr D Biol Crystallogr 60:1687-90. 2004..The active site is highly similar to those of two previously reported RPEs and provides further evidence for essential catalytic roles for several active-site residues... - "Fishing" for the functional proteomeJohn A Gerlt
Nat Biotechnol 20:786-7. 2002 - Mechanistic diversity in the RuBisCO superfamily: a novel isomerization reaction catalyzed by the RuBisCO-like protein from Rhodospirillum rubrumHeidi J Imker
Department of Microbiology and Plant Cellular and Molecular Biology Department Plant Molecular Biology Biotechnology Program, The Ohio State University, 484 West 12th Avenue, Columbus, Ohio 43210, USA
Biochemistry 47:11171-3. 2008..Disruption of the gene encoding the RLP abolishes the ability of R. rubrum to utilize 5'-methylthioadenosine as a sole sulfur source, implicating a new, as-yet-uncharacterized, pathway for sulfur salvage... 
Crystal structure and functional assignment of YfaU, a metal ion dependent class II aldolase from Escherichia coli K12Dean Rea
Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry, UK
Biochemistry 47:9955-65. 2008..Crystal structures suggest these enzymes use an Asp-His intersubunit dyad to activate a metal-bound water or hydroxide for proton transfer during catalysis...- Identification and characterization of a mandelamide hydrolase and an NAD(P)+-dependent benzaldehyde dehydrogenase from Pseudomonas putida ATCC 12633Michael J McLeish
College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, USA
J Bacteriol 185:2451-6. 2003..The mdlY and mdlD genes were isolated and expressed in Escherichia coli, and the purified gene products were characterized as a mandelamide hydrolase and an NAD(P)(+)-dependent benzaldehyde dehydrogenase, respectively... - Product deuterium isotope effect for orotidine 5'-monophosphate decarboxylase: evidence for the existence of a short-lived carbanion intermediateKrisztina Toth
Department of Chemistry, University at Buffalo, Buffalo, New York 14260, USA
J Am Chem Soc 129:12946-7. 2007
Research Grants
- STRUCTURAL BASES FOR CATALYTIC EFFICIENCY AND SUBSTRATE SPECIFICITYJohn A Gerlt; Fiscal Year: 2010....
- GENOMIC ENZYMOLOGY: OMP DECARBOXYLASE SUPRAFAMILYJOHN GERLT; Fiscal Year: 2006..4) A structural blueprint for functional diversity in the ((beta/alpha)8-barrel fold will be tested. ..
- GENOMIC ENZYMOLOGY: THE ENOLASE SUPERFAMILYJOHN GERLT; Fiscal Year: 2006..4) We will test a structural blueprint for functional diversity in the (beta/alpha)7beta-barrel fold by determining whether new functions can be generated by in vitro evolution. ..
- STRUCTURAL BASES FOR CATALYTIC EFFICIENCY AND SUBSTRATE SPECIFICITYJOHN GERLT; Fiscal Year: 2009....
- GENOMIC ENZYMOLOGY: THE CROTONASE SUPERFAMILYJOHN GERLT; Fiscal Year: 2003..5) 3-OH Isobutyryl CoA hydrolase (HIBCH) catalyzes hydrolysis of a thioester in valine catabolism. We will study HIBCH so that we can determine whether the reaction proceeds via and enolate anion or an anionic tetrahedral intermediate. ..
- GENOMIC ENZYMOLOGY--THE ENOLASE SUPERFAMILYJOHN GERLT; Fiscal Year: 2002..Dr. Gerlt and his group will investigate the mechanism of this reaction so that they can better understand the underlying catalytic strategy used by the members of the superfamily. ..