Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1992-4-2
pubmed:abstractText
A library of mutants of the catalytic subunit of the Saccharomyces cerevisiae cAMP-dependent protein kinase was screened in vitro for mutants defective in the recognition of the regulatory subunit. The mutations identified were mapped onto the three-dimensional structure of the mouse catalytic subunit with a peptide inhibitor. Mutations defective in the recognition of both the regulatory subunit and the peptide substrate Leu-Arg-Arg-Ala-Ser-Leu-Gly (Kemptide) mapped to the peptide-binding site shared by all substrates and inhibitors of the catalytic subunit and functionally define the binding site for the autoinhibitor sequence in the hinge region of the regulatory subunit. Mutants defective only in the recognition of the regulatory subunit identified residues that comprise additional binding sites for the regulatory subunit. The majority of these residues are clustered on the surface of the catalytic subunit in a region flanking the distal portion of the autoinhibitor/peptide-binding site. The simultaneous substitution of Lys233, Asp237, Lys257, and Lys261 in this region caused a 260-fold decrease in affinity for the regulatory subunit, whereas the catalytic efficiency toward Kemptide decreased by only 1.8-fold. The substitution of autophosphorylated Thr241, also in this region, and the 3 residues interacting with the phosphate also caused an unregulated phenotype.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
267
pubmed:geneSymbol
LEU2, TPK
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4806-14
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Systematic mutational analysis of cAMP-dependent protein kinase identifies unregulated catalytic subunits and defines regions important for the recognition of the regulatory subunit.
pubmed:affiliation
Department of Protein Engineering, Genentech Inc., South San Francisco, California 94080.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't