Document Detail

AlF3 mimics the transition state of protein phosphorylation in the crystal structure of nucleoside diphosphate kinase and MgADP.
MedLine Citation:
PMID:  9108019     Owner:  NLM     Status:  MEDLINE    
Nucleoside diphosphate kinase reversibly transfers the gamma-phosphate of ATP onto its active site histidine. We have investigated the transition state of histidine phosphorylation with the high-resolution crystal structures of the enzyme from Dictyostelium discoideum with MgADP and either aluminium or beryllium fluoride. The bound aluminium fluoride species is the neutral species AlF3 and not the more common AlF4-. AlF3 forms a trigonal bipyramid that makes it an accurate analog of the transition state of the gamma-phosphate of ATP undergoing transfer to the catalytic histidine. Its axial ligands are a histidine nitrogen and a beta-phosphate oxygen. Beryllium fluoride also binds at the same position and with the same ligands but in a tetrahedral geometry resembling the Michaelis complex rather than the transition state. The two x-ray structures show explicit enzyme-substrate interactions that discriminate between the ground and the transition states of the reaction. They also illustrate the partially dissociative geometry of the transition state of phosphoryl transfer and demonstrate the potential applications of metallofluorides for the study of kinase mechanisms.
Y W Xu; S Moréra; J Janin; J Cherfils
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  94     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-05-22     Completed Date:  1997-05-22     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3579-83     Citation Subset:  IM    
Laboratoire d'Enzymologie et de Biochimie Structurales, Unité Propre de Recherche 9063 Centre National de la Recherche Scientifique, Gif Sur Yvette, France.
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MeSH Terms
Adenosine Diphosphate / chemistry
Aluminum Compounds / chemistry
Nucleoside-Diphosphate Kinase / chemistry*
Protein Conformation
Reg. No./Substance:
0/Aluminum Compounds; 58-64-0/Adenosine Diphosphate; EC Kinase

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