Lys17 in the 'lasso' peptide lariatin A is responsible for anti-mycobacterial activity.
C-terminal-lacking fragments of the anti-mycobacterial peptide lariatin A were obtained by hydrolysis using carboxypeptidase P and their anti-mycobacterial activities were evaluated. Lys17 was found to be essential for their antimicrobial activity. A molecular dynamics simulation, with explicit water molecules, helped determine the structural characteristics of Lys17 of lariatin A. The simulation revealed the dynamic formation and deformation of a salt bridge between the N(xi) atom of Lys17 and the carboxyl group of C-terminal Pro18, which is deemed to be crucial for the compound's anti-mycobacterial activity.
Iwatsuki
Masato
M
Center for Basic Research, Kitasato University, Shirokane, Minato-ku, Tokyo, Japan.
Koizumi
Yukio
Y
Gouda
Hiroaki
H
Hirono
Shuichi
S
Tomoda
Hiroshi
H
Omura
Satoshi
S
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D002268:Carboxypeptidases / Q000378:metabolism; D003198:Computer Simulation; D008239:Lysine / Q000737:chemistry*; D009161:Mycobacterium / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011487:Protein Conformation
D000900:Anti-Bacterial Agents; D010456:Peptides, Cyclic; C522551:lariatin A; C025427:carboxypeptidase P; D002268:Carboxypeptidases; D008239:Lysine