Lys17 in the 'lasso' peptide lariatin A is responsible for anti-mycobacterial activity

Masato Iwatsuki; Yukio Koizumi; Hiroaki Gouda; Shuichi Hirono; Hiroshi Tomoda; Satoshi Omura

doi:10.1016/j.bmcl.2009.03.033

Lys17 in the 'lasso' peptide lariatin A is responsible for anti-mycobacterial activity

Bioorg Med Chem Lett. 2009 May 15;19(10):2888-90. doi: 10.1016/j.bmcl.2009.03.033. Epub 2009 Mar 14.

Authors

Masato Iwatsuki¹, Yukio Koizumi, Hiroaki Gouda, Shuichi Hirono, Hiroshi Tomoda, Satoshi Omura

Affiliation

¹ Center for Basic Research, Kitasato University, Shirokane, Minato-ku, Tokyo, Japan.

PMID: 19362475
DOI: 10.1016/j.bmcl.2009.03.033

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / isolation & purification
Anti-Bacterial Agents / pharmacology
Carboxypeptidases / metabolism
Computer Simulation
Lysine / chemistry*
Mycobacterium / drug effects*
Peptides, Cyclic / chemistry*
Peptides, Cyclic / isolation & purification
Peptides, Cyclic / pharmacology
Protein Conformation

Substances

Anti-Bacterial Agents
Peptides, Cyclic
lariatin A
carboxypeptidase P
Carboxypeptidases
Lysine