1mux
From Proteopedia
(New page: 200px<br /><applet load="1mux" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mux" /> '''SOLUTION NMR STRUCTURE OF CALMODULIN/W-7 COM...) |
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'''SOLUTION NMR STRUCTURE OF CALMODULIN/W-7 COMPLEX: THE BASIS OF DIVERSITY IN MOLECULAR RECOGNITION, 30 STRUCTURES'''<br /> | '''SOLUTION NMR STRUCTURE OF CALMODULIN/W-7 COMPLEX: THE BASIS OF DIVERSITY IN MOLECULAR RECOGNITION, 30 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The solution structure of calcium-bound calmodulin (CaM) complexed with an | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1MUX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis] with CA and WW7 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1MUX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=WW7:'>WW7</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MUX OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mase, T.]] | [[Category: Mase, T.]] | ||
[[Category: Osawa, M.]] | [[Category: Osawa, M.]] | ||
| - | [[Category: Swindells, M | + | [[Category: Swindells, M B.]] |
[[Category: Tanaka, T.]] | [[Category: Tanaka, T.]] | ||
[[Category: Tanikawa, J.]] | [[Category: Tanikawa, J.]] | ||
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[[Category: w-7]] | [[Category: w-7]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:59:15 2008'' |
Revision as of 11:59, 21 February 2008
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SOLUTION NMR STRUCTURE OF CALMODULIN/W-7 COMPLEX: THE BASIS OF DIVERSITY IN MOLECULAR RECOGNITION, 30 STRUCTURES
Overview
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.
About this Structure
1MUX is a Single protein structure of sequence from Xenopus laevis with and as ligands. Full crystallographic information is available from OCA.
Reference
Solution structure of calmodulin-W-7 complex: the basis of diversity in molecular recognition., Osawa M, Swindells MB, Tanikawa J, Tanaka T, Mase T, Furuya T, Ikura M, J Mol Biol. 1998 Feb 13;276(1):165-76. PMID:9514729
Page seeded by OCA on Thu Feb 21 13:59:15 2008
Categories: Single protein | Xenopus laevis | Furuya, T. | Ikura, M. | Mase, T. | Osawa, M. | Swindells, M B. | Tanaka, T. | Tanikawa, J. | CA | WW7 | Calcium-binding | Calmodulin | Complex (calmodulin/inhibitor) | Naphthalenesulfonamide | Nmr | W-7
