Solution Structure of Polytheonamide B, a Highly Cytotoxic Nonribosomal Polypeptide from Marine Sponge

被引：67

作者：

Hamada, Toshiyuki ^{[1
,6
,8
]}

Matsunaga, Shigeki ^{[1
]}

Fujiwara, Masako ^{[5
,7
]}

Fujita, Kenichi ^{[7
]}

Hirota, Hiroshi ^{[8
]}

Schmucki, Roland ^{[3
,4
]}

Guentert, Peter ^{[3
,4
]}

Fusetani, Nobuhiro ^{[1
,2
]}

机构：

[1] Univ Tokyo, Grad Sch Agr & Life Sci, Lab Aquat Nat Prod Chem, Bunkyo Ku, Tokyo 1138657, Japan

[2] Hokkaido Univ, Grad Sch Fisheries Sci, Hakodate, Hokkaido 0418611, Japan

[3] Goethe Univ Frankfurt, Frankfurt Inst Adv Studies, D-60438 Frankfurt, Germany

[4] Goethe Univ Frankfurt, Ctr Biomol Magnet Resonance, Inst Biophys Chem, D-60438 Frankfurt, Germany

[5] Tohoku Univ, Grad Sch Pharmaceut Sci, Aoba Ku, Sendai, Miyagi 9808578, Japan

[6] Kagoshima Univ, Grad Sch Sci & Engn, Kagoshima 8900065, Japan

[7] JEOL DATUM LTD, Tokyo 1960022, Japan

[8] RIKEN, Genom Sci Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2010年 / 132卷 / 37期

关键词：

TORSION ANGLE DYNAMICS; MOLECULAR-DYNAMICS; NMR STRUCTURE; BIOLOGICAL MACROMOLECULES; GRAMICIDIN CHANNEL; THEONELLA-SWINHOEI; PROTEIN; ASSIGNMENT; PROGRAM; SIMULATION;

D O I：

10.1021/ja104616z

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Polytheonamide B (pTB), a highly cytotoxic polypeptide, is one of the most unusual nonribosomal peptides of sponge origin. pTB is a linear 48-residue peptide with alternating D- and L-amino acids and contains a total of eight types of nonproteinogenic amino acids. To investigate the mechanisms underlying its cytotoxic activity, we determined the three-dimensional structure of pTB by NMR spectroscopy, structure calculation, and energy minimization. pTB adopts a single right-handed beta(6.3)-helical structure in a 1:1 mixture of methanol/chloroform with a length of approximately 45 angstrom and a hydrophilic pore of ca. 4 angstrom inner diameter. These features indicate that pTB molecules form transmembrane channels that permeate monovalent cations as gramicidin A channels do. The strong cytotoxicity of pTB can be ascribed to its ability to form single molecule channels through biological membranes.

引用

页码：12941 / 12945

页数：5

共 35 条

[1] Gramicidin channels [J].