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Article: GTP cyclohydrolase II structure and mechanism

TitleGTP cyclohydrolase II structure and mechanism
Authors
Issue Date2005
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2005, v. 280 n. 44, p. 36912-36919 How to Cite?
AbstractGTP cyclohydrolase II converts GTP to 2,5-diamino-6-β-ribosyl-4(3N)- pyrimidinone 5′-phosphate, formate and pyrophosphate, the first step in riboflavin biosynthesis. The essential role of riboflavin in metabolism and the absence of GTP cyclohydrolase II in higher eukaryotes makes it a potential novel selective antimicrobial drug target. GTP cyclohydrolase II catalyzes a distinctive overall reaction from GTP cyclohydrolase I; the latter converts GTP to dihydroneopterin triphosphate, utilized in folate and tetrahydrobiopterin biosynthesis. The structure of GTP cyclohydrolase II determined at 1.54-Å resolution reveals both a different protein fold to GTP cyclohydrolase I and distinctive molecular recognition determinants for GTP; although in both enzymes there is a bound catalytic zinc. The GTP cyclohydrolase II-GMPCPP complex structure shows Arg128 interacting with the α-phosphonate, and thus in the case of GTP, Arg128 is positioned to act as the nucleophile for pyrophosphate release and formation of the proposed covalent guanylyl-GTP cyclohydrolase II intermediate. Tyr105 is identified as playing a key role in GTP ring opening; it is hydrogen-bonded to the zinc-activated water molecule, the latter being positioned for nucleophilic attack on the guanine C-8 atom. Although GTP cyclohydrolase I and GTP cyclohydrolase II both use a zinc ion for the GTP ring opening and formate release, different residues are utilized in each case to catalyze this reaction step. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/171739
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorRen, Jen_US
dc.contributor.authorKotaka, Men_US
dc.contributor.authorLockyer, Men_US
dc.contributor.authorLamb, HKen_US
dc.contributor.authorHawkins, ARen_US
dc.contributor.authorStammers, DKen_US
dc.date.accessioned2012-10-30T06:16:43Z-
dc.date.available2012-10-30T06:16:43Z-
dc.date.issued2005en_US
dc.identifier.citationJournal Of Biological Chemistry, 2005, v. 280 n. 44, p. 36912-36919en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10722/171739-
dc.description.abstractGTP cyclohydrolase II converts GTP to 2,5-diamino-6-β-ribosyl-4(3N)- pyrimidinone 5′-phosphate, formate and pyrophosphate, the first step in riboflavin biosynthesis. The essential role of riboflavin in metabolism and the absence of GTP cyclohydrolase II in higher eukaryotes makes it a potential novel selective antimicrobial drug target. GTP cyclohydrolase II catalyzes a distinctive overall reaction from GTP cyclohydrolase I; the latter converts GTP to dihydroneopterin triphosphate, utilized in folate and tetrahydrobiopterin biosynthesis. The structure of GTP cyclohydrolase II determined at 1.54-Å resolution reveals both a different protein fold to GTP cyclohydrolase I and distinctive molecular recognition determinants for GTP; although in both enzymes there is a bound catalytic zinc. The GTP cyclohydrolase II-GMPCPP complex structure shows Arg128 interacting with the α-phosphonate, and thus in the case of GTP, Arg128 is positioned to act as the nucleophile for pyrophosphate release and formation of the proposed covalent guanylyl-GTP cyclohydrolase II intermediate. Tyr105 is identified as playing a key role in GTP ring opening; it is hydrogen-bonded to the zinc-activated water molecule, the latter being positioned for nucleophilic attack on the guanine C-8 atom. Although GTP cyclohydrolase I and GTP cyclohydrolase II both use a zinc ion for the GTP ring opening and formate release, different residues are utilized in each case to catalyze this reaction step. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.en_US
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.subject.meshBinding Sitesen_US
dc.subject.meshCrystallizationen_US
dc.subject.meshCrystallography, X-Rayen_US
dc.subject.meshEscherichia Coli - Enzymology - Geneticsen_US
dc.subject.meshGtp Cyclohydrolase - Chemistry - Genetics - Metabolismen_US
dc.subject.meshGuanosine Triphosphate - Analogs & Derivatives - Metabolismen_US
dc.subject.meshMolecular Structureen_US
dc.subject.meshProtein Conformationen_US
dc.subject.meshTyrosine - Metabolismen_US
dc.subject.meshZinc - Metabolismen_US
dc.titleGTP cyclohydrolase II structure and mechanismen_US
dc.typeArticleen_US
dc.identifier.emailKotaka, M:masayo@hku.hken_US
dc.identifier.authorityKotaka, M=rp00293en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1074/jbc.M507725200en_US
dc.identifier.pmid16115872-
dc.identifier.scopuseid_2-s2.0-27744517816en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-27744517816&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume280en_US
dc.identifier.issue44en_US
dc.identifier.spage36912en_US
dc.identifier.epage36919en_US
dc.identifier.isiWOS:000232901800047-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridRen, J=7403083572en_US
dc.identifier.scopusauthoridKotaka, M=6604073578en_US
dc.identifier.scopusauthoridLockyer, M=36947976500en_US
dc.identifier.scopusauthoridLamb, HK=7103263399en_US
dc.identifier.scopusauthoridHawkins, AR=7102975292en_US
dc.identifier.scopusauthoridStammers, DK=34573122600en_US

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