Document Detail

Changes in MM-CK conformational mobility upon formation of the ADP-Mg(2+)-NO(3)(-)-creatine transition state analogue complex as detected by hydrogen/deuterium exchange.
MedLine Citation:
PMID:  14622006     Owner:  NLM     Status:  MEDLINE    
In the presence of ADP, Mg(2+), creatine, and the planar nitrate ion, creatine kinase isoenzymes undergo significant structural changes accompanying the formation of a very stable transition state analogue complex (TSAC). We have compared, by using hydrogen/deuterium exchange followed by proteolysis of the labeled enzyme and mass spectrometric analysis of the peptic peptides, the backbone dynamics fluctuations of the free enzyme and those of the TSAC. In most peptides, exchange is not affected by ligand binding, except that observed in seven areas located in or at the entrance to the active site, where some protection is detected. On the basis of a comparison with the three-dimensional structures of free or liganded guanidino kinases, four of these peptides (residues 54-72, 226-234, 287-311, and 315-333) can be considered part of the substrate binding site. The other three (residues 162-186, 193-201, and 202-224) are not directly involved in the binding of substrates and are located in a dynamic domain, which allows the enzyme to properly align the substrates for optimal catalysis.
Hortense Mazon; Olivier Marcillat; Eric Forest; Christian Vial
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemistry     Volume:  42     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-11-18     Completed Date:  2004-01-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13596-604     Citation Subset:  IM    
UMR CNRS 5013, Biomembranes et enzymes associés, Université Claude Bernard Lyon 1, 43, boulevard du 11 Novembre 1918, 69622 Villeurbanne cedex, France.
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MeSH Terms
Adenosine Diphosphate / chemistry*,  metabolism
Amino Acid Sequence
Binding Sites
Creatine / chemistry*,  metabolism
Creatine Kinase / chemistry*,  metabolism
Deuterium Exchange Measurement
Hydrogen / chemistry
Magnesium / chemistry*,  metabolism
Models, Molecular
Molecular Sequence Data
Muscles / enzymology
Nitrates / chemistry*,  metabolism
Pepsin A / chemistry
Peptide Fragments / analysis,  chemistry
Protein Conformation
Spectrometry, Mass, Electrospray Ionization
Reg. No./Substance:
0/Isoenzymes; 0/Nitrates; 0/Peptide Fragments; 1333-74-0/Hydrogen; 57-00-1/Creatine; 58-64-0/Adenosine Diphosphate; 7439-95-4/Magnesium; EC Kinase; EC A

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