Rabbit skeletal muscle myosin light chain kinase. The calmodulin binding domain as a potential active site-directed inhibitory domain.

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Publication Type Journal Article
School or College College of Pharmacy; School of Medicine
Department Biomedical Informatics; Biochemistry; Pharmacology & Toxicology
Creator Blumenthal, Donald K.
Other Author Kennelly, Peter J.; Edelman, Arthur M.; Krebs, Edwin G.
Title Rabbit skeletal muscle myosin light chain kinase. The calmodulin binding domain as a potential active site-directed inhibitory domain.
Date 1987-09-05
Description A synthetic peptide modeled after the calmodulin (CaM)-binding domain of rabbit skeletal muscle myosin light chain kinase, Lys-Arg-Arg-Trp-Lys5-Lys-Asn-Phe-Ile-Ala10-Val-Ser-Ala-Ala-+ ++Asn15-Arg-Phe-Glycyl amide (M5), inhibited the CaM-independent chymotryptic fragment of the enzyme, C35 (Edelman, A. M., Takio, K., Blumenthal, D. K., Hansen, R. S., Walsh, K. A., Titani, K., and Krebs, E. G. (1985) J. Biol. Chem. 260, 11275-11285), with a Ki of 3.2 +/- 2.1 microM. Inhibition was competitive with respect to the peptide substrate Lys-Lys-Arg-Ala-Ala5-Arg-Ala-Thr-Ser-Asn10-Val-Phe-Ala and was of the noncompetitive linear mixed type with respect to ATP. M5 and homologues with a serine residue substituted at positions 9, 13, or 14 were phosphorylated with the following order of preference: M5(Ser9) greater than M5(Ser13) much greater than M5(Ser14) greater than M5. The order of preference observed agreed with that predicted by comparison of the sequence of these peptides with the phosphorylation sites of myosin P-light chains. Both inhibition of C35 by M5 and phosphorylation of M5 and its serine-substituted homologues were severely curtailed by the addition of a stoichiometric excess of CaM over peptide. Thus, synthetic peptides modeled after the CaM-binding domain of skeletal muscle myosin light chain kinase can function as calmodulin-regulated active site-directed inhibitors of the enzyme.
Type Text
Publisher American Society for Biochemistry and Molecular Biology (ASBMB)
Volume 262
Issue 25
First Page 11958
Last Page 11963
Subject Synthetic Peptide
Subject MESH Binding Sites; Calmodulin; Macromolecular Substances; Muscles; Myosin-Light-Chain Kinase; Phosphorylation; Rabbits
Language eng
Bibliographic Citation Kennelly PJ, Edelman AM, Blumenthal DK, Krebs EG. Rabbit skeletal muscle myosin light chain kinase. The calmodulin binding domain as a potential active site-directed inhibitory domain. J Biol Chem. 1987 Sep 5;262(25):11958-63. Retrieved August 31, 2006 from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=3624242&query_hl=16&itool=pubmed_docsum
Rights Management Copyright © American Society for Biochemistry and Molecular Biology, J Biol Chem., 262,11958-11963,1987.
Format Medium application/pdf
Identifier ir-main,364
ARK ark:/87278/s6m623p4
Setname ir_uspace
Date Created 2012-06-13
Date Modified 2012-06-13
ID 705049
Reference URL https://collections.lib.utah.edu/ark:/87278/s6m623p4
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