title: 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.
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.
authors.affiliation: Tokyo Research Laboratories, Kyowa Hakko Kogyo Co. Ltd, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Katahira
authors.forename: M
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuda
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors*; D010455:Peptides; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013302:Streptomyces / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; C100562:MS 271; D010455:Peptides; D010456:Peptides, Cyclic; C094261:siamycin II; C087120:RES 701-1; C085040:RP 71955; D009219:Myosin-Light-Chain Kinase