Source:http://linkedlifedata.com/resource/pubmed/id/15906320
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2005-7-18
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| pubmed:databankReference | |
| pubmed:abstractText |
The mechanism of the hydrolysis reaction of guanosine triphosphate (GTP) by the protein complex Ras-GAP (p21(ras) - p120(GAP)) has been modeled by the quantum mechanical-molecular mechanical (QM/MM) and ab initio quantum calculations. Initial geometry configurations have been prompted by atomic coordinates of a structural analog (PDBID:1WQ1). It is shown that the minimum energy reaction path is consistent with an assumption of two-step chemical transformations. At the first stage, a unified motion of Arg789 of GAP, Gln61, Thr35 of Ras, and the lytic water molecule results in a substantial spatial separation of the gamma-phosphate group of GTP from the rest of the molecule (GDP). This phase of hydrolysis process proceeds through the low-barrier transition state TS1. At the second stage, Gln61 abstracts and releases protons within the subsystem including Gln61, the lytic water molecule and the gamma-phosphate group of GTP through the corresponding transition state TS2. Direct quantum calculations show that, in this particular environment, the reaction GTP + H(2)O --> GDP + H(2)PO(4) (-) can proceed with reasonable activation barriers of less than 15 kcal/mol at every stage. This conclusion leads to a better understanding of the anticatalytic effect of cancer-causing mutations of Ras, which has been debated in recent years.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins p21(ras),
http://linkedlifedata.com/resource/pubmed/chemical/Water,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
1097-0134
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| pubmed:author | |
| pubmed:copyrightInfo |
(c) 2005 Wiley-Liss, Inc.
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| pubmed:issnType |
Electronic
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| pubmed:day |
15
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| pubmed:volume |
60
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
495-503
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:15906320-Catalysis,
pubmed-meshheading:15906320-Computational Biology,
pubmed-meshheading:15906320-Genes, ras,
pubmed-meshheading:15906320-Guanosine Triphosphate,
pubmed-meshheading:15906320-Humans,
pubmed-meshheading:15906320-Hydrolysis,
pubmed-meshheading:15906320-Macromolecular Substances,
pubmed-meshheading:15906320-Models, Molecular,
pubmed-meshheading:15906320-Molecular Conformation,
pubmed-meshheading:15906320-Mutation,
pubmed-meshheading:15906320-Oxygen,
pubmed-meshheading:15906320-Protein Binding,
pubmed-meshheading:15906320-Protein Conformation,
pubmed-meshheading:15906320-Proteomics,
pubmed-meshheading:15906320-Proto-Oncogene Proteins p21(ras),
pubmed-meshheading:15906320-Static Electricity,
pubmed-meshheading:15906320-Structure-Activity Relationship,
pubmed-meshheading:15906320-Thermodynamics,
pubmed-meshheading:15906320-Water,
pubmed-meshheading:15906320-ras Proteins
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| pubmed:year |
2005
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| pubmed:articleTitle |
QM/MM modeling the Ras-GAP catalyzed hydrolysis of guanosine triphosphate.
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| pubmed:affiliation |
Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow, Russian Federation.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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