Description
Calmodulin is a calcium-
dependent protein that regulates the activity of a diverse array of enzymes, ion channels, and other proteins and thus has diverse roles in cell function. W-
7 is a cell-
permeable antagonist of calmodulin (K
i = 11 μM). Two molecules of W-
7 bind to calcium-
binding domains in each calmodulin molecule, blocking its interaction with target proteins. W-
7 also associates, at lower affinities, with calcium-
binding domains of other proteins, including troponin C and myosin light chain kinase (K
i = 70 and 300 μM, respectively).
Chemical Properties
White Crystalline Solid
Uses
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride has been used to study its effect of on coated pit staining.
Uses
W7 is a vascular relaxing agent which affects vascular smooth muscle actomyosin. W7, an inhibitor of actomyosin superprecipitation, produces relaxation of isolated rabbit arterial strips and antagonizes the contraction of the strips induced by various contractile agonists. W7 is also a calmodulin antagonist that binds to calmodulin and inhibits Ca2+/calmodulin-regulated enzyme activities.
General Description
A cell-permeable and reversible calmodulin antagonist that inhibits myosin light chain kinase (IC
50 = 51 μM) and Ca
2+-calmodulin-dependent phosphodiesterase (IC
50 = 28 μM).
Biological Activity
Calmodulin antagonist. Inhibits Ca 2+ -calmodulin-dependent phosphodiesterase (IC 50 = 28 μ M) and myosin light chain kinase (IC 50 = 51 μ M).
Biochem/physiol Actions
Cell permeable: yes
References
[1] G. BENAIM A V. Phosphorylation of calmodulin. Functional implications.[J]. European journal of biochemistry, 2002, 61 1: 3619-3631. DOI:
10.1046/j.1432-1033.2002.03038.x[2] D CHIN A R M. Calmodulin: a prototypical calcium sensor.[J]. Trends in Cell Biology, 2000, 10 8: 322-328. DOI:
10.1016/s0962-8924(00)01800-6[3] OSAWA M, SWINDELLS M, TANIKAWA J, et al. SOLUTION NMR STRUCTURE OF CALMODULIN/W-7 COMPLEX: THE BASIS OF DIVERSITY IN MOLECULAR RECOGNITION, 30 STRUCTURES[C]. 1998: 0. DOI:
10.2210/pdb1mux/pdb[4] H HIDAKA. N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist, inhibits cell proliferation.[J]. Proceedings of the National Academy of Sciences of the United States of America, 1981, 78 7: 4354-4357. DOI:
10.1073/pnas.78.7.4354[5] BISHOW B ADHIKARI Kuan W. Interplay of troponin- and Myosin-based pathways of calcium activation in skeletal and cardiac muscle: the use of W7 as an inhibitor of thin filament activation.[J]. Biophysical journal, 2004, 86 1 Pt 1: 359-370. DOI:
10.1016/s0006-3495(04)74112-0[6] RYAN M. B. HOFFMAN Brian D S. Structure of the Inhibitor W7 Bound to the Regulatory Domain of Cardiac Troponin C[J]. Biochemistry Biochemistry, 2009, 48 24: 5541-5552. DOI:
10.1021/bi9001826
