Intrasteric regulation of myosin light chain kinase

J. K. Krueger, R. C. Padre, J. T. Stull

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Ca2+/calmodulin activates myosin light chain kinase by reversal of an autoinhibited state. The effects of substitution mutations on calmodulin activation properties implicate 4 of the 8 basic residues between the catalytic core and the calmodulin-binding domain in maintaining autoinhibition. These residues are further amino-terminal to the basic residues comprising the previously proposed pseudosubstrate sequence and suggest involvement of the connecting region in intrasteric autoinhibition. The pseudosubstrate model for autoinhibition proposes that basic residues within the autoinhibitory region mimic basic residues in the substrate and bind to defined acidic residues within the catalytic core. Charge reversal mutations of these specific acidic residues, however, had little or no effect on the K(m) value for regulatory light chain. From a total of 20 acidic residues on the surface of the substrate binding lobe of the catalytic core, 7 are implicated in binding directly or indirectly to the autoinhibitory domain but not to the light chain. Only 2 acidic residues near the catalytic site may bind to the autoinhibitory domain and the arginine at P-3 in the light chain. Exposure of these 2 residues upon calmodulin binding may be necessary and sufficient for light chain phosphorylation.

Original languageEnglish (US)
Pages (from-to)16848-16853
Number of pages6
JournalJournal of Biological Chemistry
Volume270
Issue number28
DOIs
StatePublished - 1995

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Myosin-Light-Chain Kinase
Calmodulin
Catalytic Domain
Light
Mutation
Phosphorylation
Substrates
Arginine
Substitution reactions
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Intrasteric regulation of myosin light chain kinase. / Krueger, J. K.; Padre, R. C.; Stull, J. T.

In: Journal of Biological Chemistry, Vol. 270, No. 28, 1995, p. 16848-16853.

Research output: Contribution to journalArticle

Krueger, J. K. ; Padre, R. C. ; Stull, J. T. / Intrasteric regulation of myosin light chain kinase. In: Journal of Biological Chemistry. 1995 ; Vol. 270, No. 28. pp. 16848-16853.
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