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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
26
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pubmed:dateCreated |
1996-6-7
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pubmed:abstractText |
GTP cyclohydrolase I of Escherichia coli is a torus-shaped homodecamer with D5 symmetry and catalyzes a complex ring expansion reaction conducive to the formation of dihydroneopterin triphosphate from GTP. The x-ray structure of a complex of the enzyme with the substrate analog, dGTP, bound at the active site was determined at a resolution of 3 A. In the decamer, 10 equivalent active sites are present, each of which contains a 10-A deep pocket formed by surface areas of 3 adjacent subunits. The substrate forms a complex hydrogen bond network with the protein. Active site residues were modified by site-directed mutagenesis, and enzyme activities of the mutant proteins were measured. On this basis, a mechanism of the enzyme-catalyzed reaction is proposed. Cleavage of the imidazole ring is initiated by protonation of N7 by His-179 followed by the attack of water at C8 of the purine system. Cystine Cys-110 Cys-181 may be involved in this reaction step. Opening of the imidazole ring may be in concert with cleavage of the furanose ring to generate a Schiff's base from the glycoside. The gamma-phosphate of GTP may be involved in the subsequent Amadori rearrangement of the carbohydrate side chain by activating the hydroxyl group of Ser-135.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-14247678,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-1518056,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-1520321,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-1551827,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-1665332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-1985963,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-2404185,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-2584186,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-2584226,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-2862841,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-4296838,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-4904679,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-5330663,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-7473713,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-7663943,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-7798151,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-8137809,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-821948,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-8262960,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-8304099,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-8320220,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8618856-8461009
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
92
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12120-5
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8618856-Amino Acid Sequence,
pubmed-meshheading:8618856-Binding Sites,
pubmed-meshheading:8618856-Cloning, Molecular,
pubmed-meshheading:8618856-Conserved Sequence,
pubmed-meshheading:8618856-Crystallography, X-Ray,
pubmed-meshheading:8618856-Escherichia coli,
pubmed-meshheading:8618856-GTP Cyclohydrolase,
pubmed-meshheading:8618856-Hydrogen Bonding,
pubmed-meshheading:8618856-Kinetics,
pubmed-meshheading:8618856-Macromolecular Substances,
pubmed-meshheading:8618856-Models, Molecular,
pubmed-meshheading:8618856-Models, Structural,
pubmed-meshheading:8618856-Molecular Sequence Data,
pubmed-meshheading:8618856-Mutagenesis, Site-Directed,
pubmed-meshheading:8618856-Point Mutation,
pubmed-meshheading:8618856-Protein Structure, Secondary,
pubmed-meshheading:8618856-Recombinant Proteins,
pubmed-meshheading:8618856-Structure-Activity Relationship
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pubmed:year |
1995
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pubmed:articleTitle |
Active site topology and reaction mechanism of GTP cyclohydrolase I.
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pubmed:affiliation |
Max-Planck-Institut für Biochemie, Martinsried, Federal Republic of Germany.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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