7CP1

Crystal structure of isocitrate lyase in complex with succinate and itaconate

7CP1 の概要

• エントリーDOI: 10.2210/pdb7cp1/pdb
• 分子名称: Isocitrate lyase, SUCCINIC ACID, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: glyoxylate cycle, isocitrate lyase, succinate, itaconate, mycobacterium tuberculosis, lyase
• 由来する生物種: Mycobacterium tuberculosis H37Rv
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 96707.86

構造登録者

Kwon, S.,Park, H.H. (登録日: 2020-08-05, 公開日: 2021-05-19, 最終更新日: 2023-11-29)

主引用文献

Kwon, S.,Chun, H.L.,Ha, H.J.,Lee, S.Y.,Park, H.H.
Heterogeneous multimeric structure of isocitrate lyase in complex with succinate and itaconate provides novel insights into its inhibitory mechanism.
Plos One, 16:e0251067-e0251067, 2021

PubMed Abstract: During the glyoxylate cycle, isocitrate lyases (ICLs) catalyze the lysis of isocitrate to glyoxylate and succinate. Itaconate has been reported to inhibit an ICL from Mycobacterium tuberculosis (tbICL). To elucidate the molecular mechanism of ICL inhibition, we determined the crystal structure of tbICL in complex with itaconate. Unexpectedly, succinate and itaconate were found to bind to the respective active sites in the dimeric form of tbICL. Our structure revealed the active site architecture as an open form, although the substrate and inhibitor were bound to the active sites. Our findings provide novel insights into the conformation of tbICL upon its binding to a substrate or inhibitor, along with molecular details of the inhibitory mechanism of itaconate.

PubMed: 33951112
DOI: 10.1371/journal.pone.0251067

実験手法

X-RAY DIFFRACTION (2.58 Å)