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.
Ferrer
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A
Unit of Biochemistry, University of Barcelona, School of Pharmacy, Spain.
Caelles
C
C
Hegardt
F G
FG
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