1. MS-271, a novel inhibitor of calmodulin-activated myosin light chain kinase from Streptomyces sp.--II. Solution structure of MS-271: characteristic features of the "lasso' structure.
- Author
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Katahira R, Yamasaki M, Matsuda Y, and Yoshida M
- Subjects
- Amino Acid Sequence, Anti-Bacterial Agents chemistry, Computer Simulation, Enzyme Inhibitors chemistry, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Sequence Data, Protein Conformation, Sequence Homology, Amino Acid, Streptomyces chemistry, Myosin-Light-Chain Kinase antagonists & inhibitors, Peptides, Peptides, Cyclic chemistry
- Abstract
MS-271 is a potent inhibitor of smooth muscle myosin light chain kinase (MLCK), obtained from Streptomyces sp. In the previous paper, we reported on the isolation, structural determination and biological properties of MS-271.(1) In this paper, we report on the three-dimensional structure of MS-271 determined by 1H NMR in deuterated dimethyl sulphoxide. MS-271 consists of 21 amino acid residues with a novel internal linkage between the beta-carboxyl group of Asp9 and the alpha-amino group of Cysl, and two disulfide bonds, Cys1-Cys13 and Cys7-Cys19. The internal linkage between the side chain of Asp9 and the alpha-amino group of the N-terminal residue is the same as that of the endothelin B receptor selective antagonist, RES-701-1, that we previously reported. The structural calculations involved the combined use of distance geometry and simulated annealing calculations. The results indicated that MS-271 undergoes extraordinary folding, i.e. the "tail' (Phe10-dTrp21) passes through the "ring' region (Cys1-Asp9) ("lasso' structure). This folding of MS-271 turned out to be the same as the "lasso' structure of RES-701-1. The features of this "lasso' structure are discussed on the basis of comparison between the structures of MS-271 and RES-701-1.
- Published
- 1996
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