1aj1

From Proteopedia

Revision as of 13:43, 5 November 2007

NMR STRUCTURE OF THE LANTIBIOTIC ACTAGARDINE, 15 STRUCTURES

Overview

The three-dimensional solution structure of the lantibiotic actagardine, was determined at high resolution by homonuclear and heteronuclear, two-dimensional and three-dimensional NMR spectroscopy in, [2H3]acetonitrile/H2O (7:3). 133 non-trivial distance and 22, torsional-angle constraints were derived from the NMR data. An ensemble of, 15 low-energy structures was calculated by distance geometry followed by, an iterative relaxation-matrix-refinement procedure. The rmsd of the, backbone coordinates with respect to the average structure was 17 pm. The, two distinct thioether ring systems 1-6 and 7-19 were even better defined, with backbone rmsd of 10 pm and 14 pm, respectively. Actagardine shows a, rigid compact globular shape based on the constraining bridging pattern, which is composed of an N-terminal lanthionine ring from residues 1-6 and, three intertwined C-terminal methyllanthionine rings comprising residues, 7-12, 9-17 and 14-19. In addition, this C-terminal ring system is, stabilised by a short antiparallel beta sheet. A feature of the, actagardine structure is the presence of two putative binding pockets. A, pocket is generated by the covalent constraints of the C-terminal, thioether ring system. The rim of this pocket is built up by a loop, structure comprising residues 12-19, whose backbone amide protons are all, directed to the centre of the pocket. The second pocket is formed by an, L-shaped orientation of the N-terminal and C-terminal thioether ring, systems. The only two hydrophilic amino acid residues of actagardine, Glu11 and Ser2, are directed to this pocket. A region of high sequence, similarity with the related lantibiotic mersacidin is located exactly at, the position of the second pocket (residues 3-12). This suggests that the, second pocket is responsible for the antibiotic mode of action of, actagardine and mersacidin as inhibitors of the murein biosynthesis of, gram-positive bacteria.

About this Structure

1AJ1 is a Single protein structure of sequence from Actinoplanes liguriae and actinoplanes garbadinensis. Structure known Active Site: MER. Full crystallographic information is available from OCA.

Reference

The three-dimensional solution structure of the lantibiotic murein-biosynthesis-inhibitor actagardine determined by NMR., Zimmermann N, Jung G, Eur J Biochem. 1997 Jun 15;246(3):809-19. PMID:9219543

Page seeded by OCA on Mon Nov 5 15:48:29 2007