« Previous Abstract"Synthesis and characterization of hexadecadienyl compounds with a conjugated diene system, sex pheromone of the persimmon fruit moth and related compounds"    Next AbstractPossible involvement of differential splicing in regulation of the activity of Arabidopsis ANP1 that is related to mitogen-activated protein kinase kinase kinases (MAPKKKs) »

J Bacteriol

Title:		Structure-activity relationship of gelatinase biosynthesis-activating pheromone of Enterococcus faecalis
Author(s):		Nishiguchi K; Nagata K; Tanokura M; Sonomoto K; Nakayama J;
Address:		"Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan"
Journal Title:		J Bacteriol
Year:		2009
Volume:		20081107
Issue:		2
Page Number:		641 - 650
DOI:		10.1128/JB.01029-08
ISSN/ISBN:		1098-5530 (Electronic) 0021-9193 (Print) 0021-9193 (Linking)
Abstract:		"The expression of pathogenicity-related extracellular proteases, namely, gelatinase and serine protease, in Enterococcus faecalis is positively regulated by a quorum-sensing system mediated by an autoinducing peptide called gelatinase biosynthesis-activating pheromone (GBAP). GBAP is an 11-amino-acid-residue cyclic peptide containing a lactone linkage. To study the structure-activity relationship of GBAP, we synthesized a series of GBAP analogues and evaluated their activities by a gelatinase-inducing assay and newly developed receptor-binding assays in which fluorescence-labeled peptides bound onto the FsrC-overexpressing Lactococcus lactis cell surface were observed by fluorescent microscopy and quantified by using a fluorophotometer. Alanine-scanning analysis of GBAP showed that the entire ring region was involved in the GBAP agonist activity, while side chains of the tail region were not strictly recognized. The alanine substitution of Phe(7) or Trp(10) almost abolished their receptor-binding abilities and GBAP agonist activities, suggesting that these two aromatic side chains are strongly involved in receptor interaction and activation. Furthermore, the Trp(10) substitution with natural and unnatural aromatic amino acids, except pentafluorophenylalanine, caused no loss of agonist activity. This suggested the importance of a negative electrostatic potential created by an pi-electron cloud on the aromatic ring surface. Structural analysis of GBAP with nuclear magnetic resonance spectroscopy revealed that the ring region adopted a hairpin-like fold and was tightly packed into a compact form. The side chain of Trp(10) was partially buried in the core structure, contributing to the stabilization of the compact form, while that of Phe(7) was extended from the core structure into the solvent and was probably directly involved in receptor binding"
Keywords:		"Bacterial Proteins/genetics/metabolism Crystallography, X-Ray Enterococcus faecalis/*chemistry/genetics/metabolism Gelatinases/metabolism Lactococcus lactis/genetics/metabolism Lactones/chemical synthesis/*chemistry/*metabolism Magnetic Resonance Spectros;"
Notes:		"MedlineNishiguchi, Kenzo Nagata, Koji Tanokura, Masaru Sonomoto, Kenji Nakayama, Jiro eng Research Support, Non-U.S. Gov't 2008/11/11 J Bacteriol. 2009 Jan; 191(2):641-50. doi: 10.1128/JB.01029-08. Epub 2008 Nov 7"