6OZ6

Crystal structure of MraY bound to 3'-hydroxymureidomycin A

6OZ6 の概要

• エントリーDOI: 10.2210/pdb6oz6/pdb
• 分子名称: MraYAA nanobody, Phospho-N-acetylmuramoyl-pentapeptide-transferase, (2~{S})-2-[[(2~{S})-1-[[(2~{S},3~{S})-3-[[(2~{S})-2-azanyl-3-(3-hydroxyphenyl)propanoyl]-methyl-amino]-1-[[(~{Z})-[(3~{S},4~{R},5~{R})-5-[2,4-bis(oxidanylidene)pyrimidin-1-yl]-3,4-bis(oxidanyl)oxolan-2-ylidene]methyl]amino]-1-oxidanylidene-butan-2-yl]amino]-4-methylsulfanyl-1-oxidanylidene-butan-2-yl]carbamoylamino]-3-(3-hydroxyphenyl)propanoic acid (3 entities in total)
• 機能のキーワード: peptidoglycan biosynthesis, antibiotic target, integral membrane enzyme, translocase, membrane protein, membrane protein-transferase complex, membrane protein/transferase
• 由来する生物種: Lama glama; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 226620.04

構造登録者

Mashalidis, E.H.,Lee, S.Y. (登録日: 2019-05-15, 公開日: 2019-07-10, 最終更新日: 2024-11-06)

主引用文献

Mashalidis, E.H.,Kaeser, B.,Terasawa, Y.,Katsuyama, A.,Kwon, D.Y.,Lee, K.,Hong, J.,Ichikawa, S.,Lee, S.Y.
Chemical logic of MraY inhibition by antibacterial nucleoside natural products.
Nat Commun, 10:2917-2917, 2019

PubMed Abstract: Novel antibacterial agents are needed to address the emergence of global antibiotic resistance. MraY is a promising candidate for antibiotic development because it is the target of five classes of naturally occurring nucleoside inhibitors with potent antibacterial activity. Although these natural products share a common uridine moiety, their core structures vary substantially and they exhibit different activity profiles. An incomplete understanding of the structural and mechanistic basis of MraY inhibition has hindered the translation of these compounds to the clinic. Here we present crystal structures of MraY in complex with representative members of the liposidomycin/caprazamycin, capuramycin, and mureidomycin classes of nucleoside inhibitors. Our structures reveal cryptic druggable hot spots in the shallow inhibitor binding site of MraY that were not previously appreciated. Structural analyses of nucleoside inhibitor binding provide insights into the chemical logic of MraY inhibition, which can guide novel approaches to MraY-targeted antibiotic design.

PubMed: 31266949
DOI: 10.1038/s41467-019-10957-9

実験手法

X-RAY DIFFRACTION (3.7 Å)