Solution structure of calmodulin-W-7 complex: The basis of diversity in molecular recognition

Masanori Osawa, Mark B. Swindells, Jun Tanikawa, Toshiyuki Tanaka, Toshiyasu Mase, Toshio Furuya, Mitsuhiko Ikura

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

The solution structure of calcium-bound calmodulin (CaM) complexed with an antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), has been determined by multidimensional NMR spectroscopy. The structure consists of one molecule of W-7 binding to each of the two domains of CaM. In each domain, the W-7 chloronaphthalene ring interacts with four methionine methyl groups and other aliphatic or aromatic side-chains in a deep hydrophobic pocket, the site responsible for CaM binding to CaM-dependent enzymes such as myosin light chain kinases (MLCKs) and CaM kinase II. This competitive binding at the same site between W-7 and CaM-dependent enzymes suggests the mechanism by which W-7 inhibits CaM to activate the enzymes. The orientation of the W-7 naphthalene ring in the N-terminal pocket is rotated approximately 40 degrees with respect to that in the C-terminal pocket. The W-7 ring orientation differs significantly from the Trp800 indole ring of smooth muscle MLCK bound to the C-terminal pocket and the phenothiazine ring of trifluoperazine bound to the N or C-terminal pocket. These comparative structural analyses demonstrate that the two hydrophobic pockets of CaM can accommodate a variety of bulky aromatic rings, which provides a plausible structural basis for the diversity in CaM-mediated molecular recognition.

Original languageEnglish
Pages (from-to)165-176
Number of pages12
JournalJournal of Molecular Biology
Volume276
Issue number1
DOIs
Publication statusPublished - 1998 Feb 13
Externally publishedYes

Fingerprint

Calmodulin
Myosin-Light-Chain Kinase
Enzymes
Smooth Muscle Myosins
Trifluoperazine
Calcium-Calmodulin-Dependent Protein Kinases
Competitive Binding
W 7
Magnetic Resonance Spectroscopy
Calcium

Keywords

  • Calmodulin-W-7 complex
  • Molecular recognition
  • Three-dimensional solution structure
  • Van der Waals interaction

ASJC Scopus subject areas

  • Virology

Cite this

Solution structure of calmodulin-W-7 complex : The basis of diversity in molecular recognition. / Osawa, Masanori; Swindells, Mark B.; Tanikawa, Jun; Tanaka, Toshiyuki; Mase, Toshiyasu; Furuya, Toshio; Ikura, Mitsuhiko.

In: Journal of Molecular Biology, Vol. 276, No. 1, 13.02.1998, p. 165-176.

Research output: Contribution to journalArticle

Osawa, M, Swindells, MB, Tanikawa, J, Tanaka, T, Mase, T, Furuya, T & Ikura, M 1998, 'Solution structure of calmodulin-W-7 complex: The basis of diversity in molecular recognition', Journal of Molecular Biology, vol. 276, no. 1, pp. 165-176. https://doi.org/10.1006/jmbi.1997.1524
Osawa, Masanori ; Swindells, Mark B. ; Tanikawa, Jun ; Tanaka, Toshiyuki ; Mase, Toshiyasu ; Furuya, Toshio ; Ikura, Mitsuhiko. / Solution structure of calmodulin-W-7 complex : The basis of diversity in molecular recognition. In: Journal of Molecular Biology. 1998 ; Vol. 276, No. 1. pp. 165-176.
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