The protein inhibitor of adenosine 3',5'-monophosphate-dependent protein kinases. the NH2-terminal portion of the peptide chain contains the inhibitory site

Demaille, J.G.; Ferraz, C.; Fischer, E.H.

Biochimica et Biophysica Acta 586(2): 374-383

1979


ISSN/ISBN: 0006-3002
PMID: 224942
DOI: 10.1016/0304-4165(79)90106-5
Accession: 068524728

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Abstract
The protein inhibitor of protease digestions do not abolish the inhibitory properties. This inhibitory site must contain the essential arginyl side chain(s), whereas lysyl and carboxylic side chains do not appear to be involved in the interaction with the catalytic subunit. Digestion of the COOH-terminus of the inhibitor by carboxypeptidase Y results in a doubling of the Ki value. An inhibitory pentadecapeptide (Ki = 25 nM), presumably NH2-terminal in the entire molecule, was isolated from a staphylococcal protease digest by means of gel filtration followed by ion exchange on phosphocellulose. The purified inhibitory peptide contains 2 of the 4 arginyl residues present in the entire molecule. The remarkable affinity and specificity of the protein kinase inhibitor for the catalytic subunit of 3',5'-AMP-dependent protein kinases may thus be tentatively explained on the basis of a 2-prong attachment of the inhibitor. The NH2-terminal portion of the chain would bind at the substrate binding site, whereas the COOH-terminal part would be held elsewhere.