Solution structure of polytheonamide B, a highly cytotoxic nonribosomal polypeptide from marine sponge.
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 β(6.3)-helical structure in a 1:1 mixture of methanol/chloroform with a length of approximately 45 A and a hydrophilic pore of ca. 4 A 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.
Hamada
Toshiyuki
T
Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan. thamada@sci.kagoshima-u.ac.jp
Matsunaga
Shigeki
S
Fujiwara
Masako
M
Fujita
Kenichi
K
Hirota
Hiroshi
H
Schmucki
Roland
R
Güntert
Peter
P
Fusetani
Nobuhiro
N
D000818:Animals; D032701:Biomimetics; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D020128:Inhibitory Concentration 50; D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009930:Organic Chemicals / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D012996:Solutions; D012997:Solvents / Q000737:chemistry
D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels; D009930:Organic Chemicals; D010455:Peptides; D011506:Proteins; D012996:Solutions; D012997:Solvents; C111717:polytheonamide B