7AC8

Molecular basis for the unique allosteric activation mechanism of the heterodimeric imidazole glycerol phosphate synthase complex.

7AC8 の概要

• エントリーDOI: 10.2210/pdb7ac8/pdb
• 分子名称: Imidazole glycerol phosphate synthase subunit HisF, Imidazole glycerol phosphate synthase subunit HisH, [(2R,3S,4R,5R)-5-[4-aminocarbonyl-5-[(E)-[[(2R,3R,4S,5R)-3,4-bis(oxidanyl)-5-(phosphonooxymethyl)oxolan-2-yl]amino]methylideneamino]imidazol-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl dihydrogen phosphate, ... (6 entities in total)
• 機能のキーワード: enzyme regulation, allostery, ensemble model, conformational changes, hisf, hish, imidazole glycerol phosphate synthase, lyase (4.3.2.10), lyase
• 由来する生物種: Thermotoga maritima; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 154809.91

構造登録者

Sung, S.,Wilmanns, M. (登録日: 2020-09-10, 公開日: 2021-05-19, 最終更新日: 2024-01-31)

主引用文献

Wurm, J.P.,Sung, S.,Kneuttinger, A.C.,Hupfeld, E.,Sterner, R.,Wilmanns, M.,Sprangers, R.
Molecular basis for the allosteric activation mechanism of the heterodimeric imidazole glycerol phosphate synthase complex.
Nat Commun, 12:2748-2748, 2021

PubMed Abstract: Imidazole glycerol phosphate synthase (HisFH) is a heterodimeric bienzyme complex operating at a central branch point of metabolism. HisFH is responsible for the HisH-catalyzed hydrolysis of glutamine to glutamate and ammonia, which is then used for a cyclase reaction by HisF. The HisFH complex is allosterically regulated but the underlying mechanism is not well understood. Here, we elucidate the molecular basis of the long range, allosteric activation of HisFH. We establish that the catalytically active HisFH conformation is only formed when the substrates of both HisH and HisF are bound. We show that in this conformation an oxyanion hole in the HisH active site is established, which rationalizes the observed 4500-fold allosteric activation compared to the inactive conformation. In solution, the inactive and active conformations are in a dynamic equilibrium and the HisFH turnover rates correlate with the population of the active conformation, which is in accordance with the ensemble model of allostery.

PubMed: 33980881
DOI: 10.1038/s41467-021-22968-6

実験手法

X-RAY DIFFRACTION (2.06 Å)