4PI9

Crystal structure of S. Aureus Autolysin E in complex with muropeptide NAM-L-ALA-D-iGLU

4PI9 の概要

• エントリーDOI: 10.2210/pdb4pi9/pdb
• 分子名称: Autolysin E, SULFATE ION, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: autolysin, glycosidase, peptidoglycan, muropeptide, hydrolase
• 由来する生物種: Staphylococcus aureus (strain Mu50 / ATCC 700699)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27097.12

構造登録者

Mihelic, M.,Renko, M.,Turk, D. (登録日: 2014-05-08, 公開日: 2015-10-14, 最終更新日: 2023-12-27)

主引用文献

Mihelic, M.,Vlahovicek-Kahlina, K.,Renko, M.,Mesnage, S.,Dobersek, A.,Taler-Vercic, A.,Jakas, A.,Turk, D.
The mechanism behind the selection of two different cleavage sites in NAG-NAM polymers.
IUCrJ, 4:185-198, 2017

PubMed Abstract: Peptidoglycan is a giant molecule that forms the cell wall that surrounds bacterial cells. It is composed of alternating -acetylglucosamine (NAG) and -acetylmuramic acid (NAM) residues connected by β-(1,4)-glycosidic bonds and cross-linked with short polypeptide chains. Owing to the increasing antibiotic resistance against drugs targeting peptidoglycan synthesis, studies of enzymes involved in the degradation of peptidoglycan, such as -acetylglucos-aminidases, may expose new, valuable drug targets. The scientific challenge addressed here is how lysozymes, muramidases which are likely to be the most studied enzymes ever, and bacterial -acetylglucosaminidases discriminate between two glycosidic bonds that are different in sequence yet chemically equivalent in the same NAG-NAM polymers. In spite of more than fifty years of structural studies of lysozyme, it is still not known how the enzyme selects the bond to be cleaved. Using macromolecular crystallography, chemical synthesis and molecular modelling, this study explains how these two groups of enzymes based on an equivalent structural core exhibit a difference in selectivity. The crystal structures of -acetylglucosaminidase autolysin E (AtlE) alone and in complex with fragments of peptidoglycan revealed that -acetylglucosaminidases and muramidases approach the substrate at alternate glycosidic bond positions from opposite sides. The recognition pocket for NAM residues in the active site of -acetylglucosaminidases may make them a suitable drug target.

PubMed: 28250957
DOI: 10.1107/S2052252517000367

実験手法

X-RAY DIFFRACTION (1.48 Å)