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Article: GTP cyclohydrolase II structure and mechanism
Title | GTP cyclohydrolase II structure and mechanism |
---|---|
Authors | |
Issue Date | 2005 |
Publisher | American 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? |
Abstract | GTP 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 Identifier | http://hdl.handle.net/10722/171739 |
ISSN | 2020 Impact Factor: 5.157 2023 SCImago Journal Rankings: 1.766 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Ren, J | en_US |
dc.contributor.author | Kotaka, M | en_US |
dc.contributor.author | Lockyer, M | en_US |
dc.contributor.author | Lamb, HK | en_US |
dc.contributor.author | Hawkins, AR | en_US |
dc.contributor.author | Stammers, DK | en_US |
dc.date.accessioned | 2012-10-30T06:16:43Z | - |
dc.date.available | 2012-10-30T06:16:43Z | - |
dc.date.issued | 2005 | en_US |
dc.identifier.citation | Journal Of Biological Chemistry, 2005, v. 280 n. 44, p. 36912-36919 | en_US |
dc.identifier.issn | 0021-9258 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/171739 | - |
dc.description.abstract | GTP 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.language | eng | en_US |
dc.publisher | American Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/ | en_US |
dc.relation.ispartof | Journal of Biological Chemistry | en_US |
dc.subject.mesh | Binding Sites | en_US |
dc.subject.mesh | Crystallization | en_US |
dc.subject.mesh | Crystallography, X-Ray | en_US |
dc.subject.mesh | Escherichia Coli - Enzymology - Genetics | en_US |
dc.subject.mesh | Gtp Cyclohydrolase - Chemistry - Genetics - Metabolism | en_US |
dc.subject.mesh | Guanosine Triphosphate - Analogs & Derivatives - Metabolism | en_US |
dc.subject.mesh | Molecular Structure | en_US |
dc.subject.mesh | Protein Conformation | en_US |
dc.subject.mesh | Tyrosine - Metabolism | en_US |
dc.subject.mesh | Zinc - Metabolism | en_US |
dc.title | GTP cyclohydrolase II structure and mechanism | en_US |
dc.type | Article | en_US |
dc.identifier.email | Kotaka, M:masayo@hku.hk | en_US |
dc.identifier.authority | Kotaka, M=rp00293 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1074/jbc.M507725200 | en_US |
dc.identifier.pmid | 16115872 | - |
dc.identifier.scopus | eid_2-s2.0-27744517816 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-27744517816&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 280 | en_US |
dc.identifier.issue | 44 | en_US |
dc.identifier.spage | 36912 | en_US |
dc.identifier.epage | 36919 | en_US |
dc.identifier.isi | WOS:000232901800047 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Ren, J=7403083572 | en_US |
dc.identifier.scopusauthorid | Kotaka, M=6604073578 | en_US |
dc.identifier.scopusauthorid | Lockyer, M=36947976500 | en_US |
dc.identifier.scopusauthorid | Lamb, HK=7103263399 | en_US |
dc.identifier.scopusauthorid | Hawkins, AR=7102975292 | en_US |
dc.identifier.scopusauthorid | Stammers, DK=34573122600 | en_US |
dc.identifier.issnl | 0021-9258 | - |