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rdf:type |
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lifeskim:mentions |
umls-concept:C0001383,
umls-concept:C0007961,
umls-concept:C0205103,
umls-concept:C0243102,
umls-concept:C0596961,
umls-concept:C1546426,
umls-concept:C1548280,
umls-concept:C1706211,
umls-concept:C1709893,
umls-concept:C2603343,
umls-concept:C2717971
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pubmed:issue |
7
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pubmed:dateCreated |
1975-12-18
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pubmed:abstractText |
The charge relay ststem and its role in the acylation of serine proteinases is studied using the partial retention of diatomic differential overlap (PRDDO) technique to perform approximate ab initio molecular orbital calculations on a model of the enzyme-substrate complex. The aspartate in the charge relay system is seen to act as the ultimate proton acceptor during the charging of the serine nucleophile. A projection of the potential energy surface is obtained in a subspace corresponding to this charge transfer and to the coupled motions of active site residues and the substrate. These results together with extended basis set results for cruder models suggest that a concerted transfer of protons from Ser-195 to His-57 and from His-57 to Asp-102 occurs with an energy barrier of 20-25 kcal/mole (84-105 kJ/mole). The subsequent nucleophilic attack on the scissile peptide linkage by the charged serine is then seen to proceed energetically downhill to the tetrahedral intermediate. The formation of the tetrahedral intermediate from the Michaelis complex is calculated to be nearly thermoneutral.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/1058476-4204227,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1058476-4372018,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1058476-4650716,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1058476-4737866,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1058476-4758115,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1058476-4821871,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1058476-5069789,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1058476-5414747,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1058476-5459201,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1058476-5764436,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1058476-5784192,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1058476-5806970,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1058476-5940964
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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 |
Jul
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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:volume |
72
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2606-10
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:1058476-Acylation,
pubmed-meshheading:1058476-Ammonia,
pubmed-meshheading:1058476-Binding Sites,
pubmed-meshheading:1058476-Calorimetry,
pubmed-meshheading:1058476-Formates,
pubmed-meshheading:1058476-Imidazoles,
pubmed-meshheading:1058476-Kinetics,
pubmed-meshheading:1058476-Models, Molecular,
pubmed-meshheading:1058476-Oxides,
pubmed-meshheading:1058476-Peptide Hydrolases,
pubmed-meshheading:1058476-Protein Binding,
pubmed-meshheading:1058476-Protein Conformation,
pubmed-meshheading:1058476-Pyridines,
pubmed-meshheading:1058476-Serine,
pubmed-meshheading:1058476-Thermodynamics
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pubmed:year |
1975
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pubmed:articleTitle |
Molecular orbital studies of enzyme activity: I: Charge relay system and tetrahedral intermediate in acylation of serine proteinases.
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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.
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