Reaction of 5'-p-fluorosulfonylbenzoyladenosine with the catalytic and AMP allosteric sites of microsomal HMG-CoA reductase kinase.
The nucleotide analogue 5-p-fluorosulfonylbenzoyladenosine reacts with rat liver microsomal 3-hydroxy-3-methylglutaryl-CoA reductase kinase, causing a rapid loss of the AMP activation capacity and a slower inactivation of the catalytic activity. The rate constant for loss of AMP activation is eleven times higher (K1 = 0.107 min-1) than the rate constant for inactivation (K2 = 0.0094 min-1). Mg-ATP protects preferentially against inactivation, while Mg-AMP at a low concentration (7.5/0.05 mM) protects preferentially against loss of the AMP activation capacity. Oppositely, Mg-ADP at a low concentration (7.5/0.05 mM) hardly protects against loss of AMP activation capacity. We conclude that microsomal reductase kinase has distinct sites for activation and catalysis.
Unit of Biochemistry, University of Barcelona, School of Pharmacy, Spain.
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Ferrer
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Caelles
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Hegardt
D055372:AMP-Activated Protein Kinases; D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000494:Allosteric Regulation; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D051381:Rats
D009097:Multienzyme Complexes; D000249:Adenosine Monophosphate; C010959:5'-(4-fluorosulfonylbenzoyl)adenosine; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D008274:Magnesium; D000241:Adenosine