1MUX

SOLUTION NMR STRUCTURE OF CALMODULIN/W-7 COMPLEX: THE BASIS OF DIVERSITY IN MOLECULAR RECOGNITION, 30 STRUCTURES

Summary for 1MUX

• Entry DOI: 10.2210/pdb1mux/pdb
• Descriptor: CALMODULIN, CALCIUM ION, N-(6-AMINOHEXYL)-5-CHLORO-1-NAPHTHALENESULFONAMIDE (3 entities in total)
• Functional Keywords: complex (calmodulin-inhibitor), calmodulin, w-7, naphthalenesulfonamide, calcium-binding
• Biological source: Xenopus laevis (African clawed frog)
• Total number of polymer chains: 1
• Total formula weight: 17563.40

Authors

Osawa, M.,Swindells, M.B.,Tanikawa, J.,Tanaka, T.,Mase, T.,Furuya, T.,Ikura, M. (deposition date: 1997-09-06, release date: 1998-10-14, Last modification date: 2024-05-22)

Primary citation

Osawa, M.,Swindells, M.B.,Tanikawa, J.,Tanaka, T.,Mase, T.,Furuya, T.,Ikura, M.
Solution structure of calmodulin-W-7 complex: the basis of diversity in molecular recognition.
J.Mol.Biol., 276:165-176, 1998

PubMed 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.

PubMed: 9514729
DOI: 10.1006/jmbi.1997.1524

Experimental method

SOLUTION NMR