| pubmed-article:10200157 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:10200157 | lifeskim:mentions | umls-concept:C0028615 | lld:lifeskim |
| pubmed-article:10200157 | lifeskim:mentions | umls-concept:C0733755 | lld:lifeskim |
| pubmed-article:10200157 | lifeskim:mentions | umls-concept:C0150305 | lld:lifeskim |
| pubmed-article:10200157 | lifeskim:mentions | umls-concept:C1561964 | lld:lifeskim |
| pubmed-article:10200157 | lifeskim:mentions | umls-concept:C1705822 | lld:lifeskim |
| pubmed-article:10200157 | lifeskim:mentions | umls-concept:C0348011 | lld:lifeskim |
| pubmed-article:10200157 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:10200157 | pubmed:issue | 15 | lld:pubmed |
| pubmed-article:10200157 | pubmed:dateCreated | 1999-5-17 | lld:pubmed |
| pubmed-article:10200157 | pubmed:abstractText | The nonenzymatic reaction of ATP with a nucleophile to generate ADP and a phosphorylated product proceeds via a dissociative transition state with little bond formation to the nucleophile. Consideration of the dissociative nature of the nonenzymatic transition state leads to the following question: To what extent can the nucleophile be activated in enzymatic phosphoryl transfer? We have addressed this question for the NDP kinase reaction. A mutant form of the enzyme lacking the nucleophilic histidine (H122G) can be chemically rescued for ATP attack by imidazole or other exogenous small nucleophiles. The ATP reaction is 50-fold faster with the wild-type enzyme, which has an imidazole nucleophile positioned for reaction by a covalent bond, than with H122G, which employs a noncovalently bound imidazole nucleophile [(kcat/KM)ATP]. Further, a 4-fold advantage for imidazole positioned in the nucleophile binding pocket created by the mutation is suggested from comparison of the reaction of H122G and ATP with an imidazole versus a water nucleophile, after correction for the intrinsic reactivities of imidazole and water toward ATP in solution. X-ray structural analysis shows no detectable rearrangement of the residues surrounding His 122 upon mutation to Gly 122. The overall rate effect of approximately 10(2)-fold for the covalent imidazole nucleophile relative to water is therefore attributed to positioning of the nucleophile with respect to the reactive phosphoryl group. This is underscored by the more deleterious effect of replacing ATP with AlphaTauPgammaS in the wild-type reaction than in the imidazole-rescued mutant reaction, as follows. For the wild-type, AlphaTauPgammaS presumably disrupts positioning between nucleophile and substrate, resulting in a large thio effect of 300-fold, whereas precise alignment is already disrupted in the mutant because there is no covalent bond to the nucleophile, resulting in a smaller thio effect of 10-fold. In summary, the results suggest a catalytic role for activation of the nucleophile by positioning in phosphoryl transfer catalyzed by NDP kinase. | lld:pubmed |
| pubmed-article:10200157 | pubmed:language | eng | lld:pubmed |
| pubmed-article:10200157 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10200157 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:10200157 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10200157 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10200157 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10200157 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10200157 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10200157 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10200157 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:10200157 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:10200157 | pubmed:issn | 0006-2960 | lld:pubmed |
| pubmed-article:10200157 | pubmed:author | pubmed-author:MeyerPP | lld:pubmed |
| pubmed-article:10200157 | pubmed:author | pubmed-author:JaninJJ | lld:pubmed |
| pubmed-article:10200157 | pubmed:author | pubmed-author:VéronMM | lld:pubmed |
| pubmed-article:10200157 | pubmed:author | pubmed-author:SchneiderBB | lld:pubmed |
| pubmed-article:10200157 | pubmed:author | pubmed-author:HerschlagDD | lld:pubmed |
| pubmed-article:10200157 | pubmed:author | pubmed-author:Deville-Bonne... | lld:pubmed |
| pubmed-article:10200157 | pubmed:author | pubmed-author:AdmiraalS JSJ | lld:pubmed |
| pubmed-article:10200157 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:10200157 | pubmed:day | 13 | lld:pubmed |
| pubmed-article:10200157 | pubmed:volume | 38 | lld:pubmed |
| pubmed-article:10200157 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:10200157 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:10200157 | pubmed:pagination | 4701-11 | lld:pubmed |
| pubmed-article:10200157 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
| pubmed-article:10200157 | pubmed:meshHeading | pubmed-meshheading:10200157... | lld:pubmed |
| pubmed-article:10200157 | pubmed:meshHeading | pubmed-meshheading:10200157... | lld:pubmed |
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| pubmed-article:10200157 | pubmed:meshHeading | pubmed-meshheading:10200157... | lld:pubmed |
| pubmed-article:10200157 | pubmed:meshHeading | pubmed-meshheading:10200157... | lld:pubmed |
| pubmed-article:10200157 | pubmed:meshHeading | pubmed-meshheading:10200157... | lld:pubmed |
| pubmed-article:10200157 | pubmed:meshHeading | pubmed-meshheading:10200157... | lld:pubmed |
| pubmed-article:10200157 | pubmed:meshHeading | pubmed-meshheading:10200157... | lld:pubmed |
| pubmed-article:10200157 | pubmed:meshHeading | pubmed-meshheading:10200157... | lld:pubmed |
| pubmed-article:10200157 | pubmed:meshHeading | pubmed-meshheading:10200157... | lld:pubmed |
| pubmed-article:10200157 | pubmed:year | 1999 | lld:pubmed |
| pubmed-article:10200157 | pubmed:articleTitle | Nucleophilic activation by positioning in phosphoryl transfer catalyzed by nucleoside diphosphate kinase. | lld:pubmed |
| pubmed-article:10200157 | pubmed:affiliation | Department of Biochemistry, Beckman Center B400, Stanford University, Stanford, California 94305-5307, USA. | lld:pubmed |
| pubmed-article:10200157 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:10200157 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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