Inhibition of protein kinase C by melittin: antagonism of binding interactions between melittin and the catalytic domain by active-site binding of MgATP.
Melittin inhibits the lipid cofactor-independent activity of protein kinase C (PKC) by directly binding to the catalytic domain in a MgATP-sensitive manner. The catalytic domains of certain PKC isozymes have a consensus sequence for a second nucleotide binding site outside their active site regions. In this report, we show that PKC isozymes containing the second nucleotide binding site motif (alpha, beta) and an isozyme lacking the motif (epsilon) all have MgATP-sensitive binding interactions with melittin. Our results support a mechanism of PKC inhibition by melittin in which active-site binding of MgATP antagonizes binding interactions between PKC and melittin.
Gravitt
K R
KR
Department of Cell Biology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Ward
N E
NE
O'Brian
C A
CA
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001923:Brain Chemistry; D016384:Consensus Sequence; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008555:Melitten / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051381:Rats
D007527:Isoenzymes; D008555:Melitten; D000255:Adenosine Triphosphate; D011493:Protein Kinase C