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 journalArticlepeer-review

142 Citations (Scopus)


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
Issue number1
Publication statusPublished - 1998 Feb 13
Externally publishedYes


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

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Structural Biology


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