2EAX

Crystal structure of human PGRP-IBETAC in complex with glycosamyl muramyl pentapeptide

2EAX の概要

• エントリーDOI: 10.2210/pdb2eax/pdb
• 関連するPDBエントリー: 2EAV
• 分子名称: Peptidoglycan recognition protein-I-beta, GLYCOSAMYL MURAMYL PENTAPEPTIDE, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-methyl 2-acetamido-3-O-[(1R)-1-carboxyethyl]-2-deoxy-beta-D-glucopyranoside, ... (4 entities in total)
• 機能のキーワード: alpha/beta, peptidoglycan-binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 54767.47

構造登録者

Cho, S. (登録日: 2007-02-03, 公開日: 2007-10-02, 最終更新日: 2024-11-13)

主引用文献

Cho, S.,Wang, Q.,Swaminathan, C.P.,Hesek, D.,Lee, M.,Boons, G.J.,Mobashery, S.,Mariuzza, R.A.
Structural insights into the bactericidal mechanism of human peptidoglycan recognition proteins
Proc.Natl.Acad.Sci.Usa, 104:8761-8766, 2007

PubMed Abstract: Peptidoglycan recognition proteins (PGRPs) are highly conserved pattern-recognition molecules of the innate immune system that bind bacterial peptidoglycans (PGNs), which are polymers of alternating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) cross-linked by short peptide stems. Human PRGPs are bactericidal against pathogenic and nonpathogenic Gram-positive bacteria, but not normal flora bacteria. Like certain glycopeptide antibiotics (e.g., vancomycin), PGRPs kill bacteria by directly interacting with their cell wall PGN, thereby interfering with PGN maturation. To better understand the bactericidal mechanism of PGRPs, we determined the crystal structure of the C-terminal PGN-binding domain of human PGRP-I beta in complex with NAG-NAM-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala, a synthetic glycopeptide comprising a complete PGN repeat. This structure, in conjunction with the previously reported NMR structure of a dimeric PGN fragment, permitted identification of major conformational differences between free and PGRP-bound PGN with respect to the relative orientation of saccharide and peptide moieties. These differences provided structural insights into the bactericidal mechanism of human PGRPs. On the basis of molecular modeling, we propose that these proteins disrupt cell wall maturation not only by sterically encumbering access of biosynthetic enzymes to the nascent PGN chains, but also by locking PGN into a conformation that prevents formation of cross-links between peptide stems in the growing cell wall.

PubMed: 17502600
DOI: 10.1073/pnas.0701453104

実験手法

X-RAY DIFFRACTION (2.1 Å)