PDBsum entry 1mqy

Antibiotic

PDB id: 1mqy

Contents

Protein chain

20 a.a.

PDB id:

1mqy

Name:

Antibiotic

Title:

Nmr solution structure of type-b lantibiotics mersacidin in dpc micelles

Structure:

Lantibiotic mersacidin. Chain: a. Synonym: type-b lantibiotics mersacidin

Source:

Bacillus sp. Hil-y85/54728. Organism_taxid: 69002. Strain: hil y-85, 54728

NMR struc:

13 models

Authors:

S.-T.Hsu,E.Breukink,G.Bierbaum,H.-G.Sahl,B.De Kruijff,R.Kaptein, N.A.Van Nuland,A.M.Bonvin

Key ref:

S.T.Hsu et al. (2003). NMR study of mersacidin and lipid II interaction in dodecylphosphocholine micelles. Conformational changes are a key to antimicrobial activity. J Biol Chem, 278, 13110-13117. PubMed id: 12562773 DOI: 10.1074/jbc.M211144200

Date:

17-Sep-02 Release date: 11-Mar-03

Protein chain

P43683  (MRSA_BACSY) -  Lantibiotic mersacidin from Bacillus sp. (strain HIL-Y85/54728)

Seq: 68 a.a.

Struc: 20 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M211144200

J Biol Chem 278:13110-13117 (2003)

PubMed id: 12562773

NMR study of mersacidin and lipid II interaction in dodecylphosphocholine micelles. Conformational changes are a key to antimicrobial activity.

S.T.Hsu, E.Breukink, G.Bierbaum, H.G.Sahl, B.de Kruijff, R.Kaptein, N.A.van Nuland, A.M.Bonvin.

ABSTRACT

Mersacidin belongs to the type B lantibiotics (lanthionine-containing antibiotics) that contain post-translationally modified amino acids and cyclic ring structures. It targets the cell wall precursor lipid II and thereby inhibits cell wall synthesis. In light of the emerging antibiotics resistance problem, the understanding of the antibacterial activity on a structural basis provides a key to circumvent this issue. Here we present solution NMR studies of mersacidin-lipid II interaction in dodecylphosphocholine (DPC) micelles. Distinct solution structures of mersacidin were determined in three different states: in water/methanol solution and in DPC micelles with and without lipid II. The structures in various sample conditions reveal remarkable conformational changes in which the junction between Ala-12 and Abu-13 (where Abu is aminobutyric acid) effectively serves as the hinge for the opening and closure of the ring structures. The DPC micelle-bound form resembles the previously determined NMR and x-ray crystal structures of mersacidin in pure methanol but substantially deviates from the other two states in our current report. The structural changes delineate the large chemical shift perturbations observed during the course of a two-step (15)N-(1)H heteronuclear single quantum coherence titration. They also modulate the surface charge distribution of mersacidin suggesting that electrostatics play a central role in the mersacidin-lipid II interaction. The observed conformational adaptability of mersacidin might be a general feature of lipid II-interacting antibiotics/peptides.

Selected figure(s)

Figure 1.
Fig. 1. Primary structures of mersacidin (A) and lipid II (B). A, post-translationally modified amino acids are highlighted in gray, and their chemical structures are depicted below. B, GlcNAc, N-acetylglucosamine; MurNAc, N-acetylmuramic acid.

Figure 8.
Fig. 8. A, representative structures (closest to average) of each structure ensemble. The Glu-17 side chain is shown in red. The hinge residue Abu-13 is shown in green. The structures were fitted on backbone heavy atoms of residues 13-20 (colored blue). The remainder of the structure is shown in gray. B, surface electrostatic potential of mersacidin in different sample conditions calculated with MOLMOL (40). Positive and negative potentials are colored blue and red, respectively. The structures are in the same orientation as in A. C, 90° rotation along the x axis of the above structures. The charge distributions reveal the increase of charge accessibility after the addition of lipid II in the hydrophobic DPC micelle solution. The structure of mersacidin in DPC micelles resembles the x-ray structure that was solved in pure methanol.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 13110-13117) copyright 2003.

Figures were selected by the author.