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Autoregulation of enzymes by pseudosubstrate prototopes: myosin light chain kinase.

Publication ,  Journal Article
Pearson, RB; Wettenhall, RE; Means, AR; Hartshorne, DJ; Kemp, BE
Published in: Science
August 19, 1988

The myosin light chain kinase requires calmodulin for activation. Tryptic cleavage of the enzyme generates an inactive 64-kilodalton (kD) fragment that can be further cleaved to form a constitutively active, calmodulin-independent, 61-kD fragment. Microsequencing and amino acid analysis of purified peptides after proteolysis of the 61- and 64-kD fragments were used to determine the amino-terminal and carboxyl-terminal sequences of the 64-kD fragment. Cleavage within the calmodulin-binding region at Arg505 generates the catalytically inactive 64-kD fragment, which is incapable of binding calmodulin. Further digestion removes a carboxyl-terminal fragment, including the pseudosubstrate sequence Ser484-Lys-Asp-Arg-Met-Lys-Lys-Tyr-Met- Ala-Arg-Arg-Lys-Trp-Gln-Lys-Thr-Gly-His-Ala-Val-Arg505 and results in a calmodulin-independent 61-kD fragment. Both the 61- and 64-kD fragments have the same primary amino-terminal sequences. These results provide direct support for the concept that the pseudosubstrate structure binds the active site and that the role of calmodulin is to modulate this interaction. Pseudosubstrates may be utilized in analogous ways by other allosterically regulated enzymes.

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Published In

Science

DOI

ISSN

0036-8075

Publication Date

August 19, 1988

Volume

241

Issue

4868

Start / End Page

970 / 973

Location

United States

Related Subject Headings

  • Substrate Specificity
  • Peptide Mapping
  • Myosin-Light-Chain Kinase
  • Muscle, Smooth
  • Molecular Sequence Data
  • General Science & Technology
  • Enzyme Activation
  • Chromatography, High Pressure Liquid
  • Calmodulin
  • Amino Acid Sequence
 

Citation

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Pearson, R. B., Wettenhall, R. E., Means, A. R., Hartshorne, D. J., & Kemp, B. E. (1988). Autoregulation of enzymes by pseudosubstrate prototopes: myosin light chain kinase. Science, 241(4868), 970–973. https://doi.org/10.1126/science.3406746
Pearson, R. B., R. E. Wettenhall, A. R. Means, D. J. Hartshorne, and B. E. Kemp. “Autoregulation of enzymes by pseudosubstrate prototopes: myosin light chain kinase.Science 241, no. 4868 (August 19, 1988): 970–73. https://doi.org/10.1126/science.3406746.
Pearson RB, Wettenhall RE, Means AR, Hartshorne DJ, Kemp BE. Autoregulation of enzymes by pseudosubstrate prototopes: myosin light chain kinase. Science. 1988 Aug 19;241(4868):970–3.
Pearson, R. B., et al. “Autoregulation of enzymes by pseudosubstrate prototopes: myosin light chain kinase.Science, vol. 241, no. 4868, Aug. 1988, pp. 970–73. Pubmed, doi:10.1126/science.3406746.
Pearson RB, Wettenhall RE, Means AR, Hartshorne DJ, Kemp BE. Autoregulation of enzymes by pseudosubstrate prototopes: myosin light chain kinase. Science. 1988 Aug 19;241(4868):970–973.
Journal cover image

Published In

Science

DOI

ISSN

0036-8075

Publication Date

August 19, 1988

Volume

241

Issue

4868

Start / End Page

970 / 973

Location

United States

Related Subject Headings

  • Substrate Specificity
  • Peptide Mapping
  • Myosin-Light-Chain Kinase
  • Muscle, Smooth
  • Molecular Sequence Data
  • General Science & Technology
  • Enzyme Activation
  • Chromatography, High Pressure Liquid
  • Calmodulin
  • Amino Acid Sequence