7BGM

Crystal structure of MtHISN2, a bifunctional enzyme from the histidine biosynthetic pathway

7BGM の概要

• エントリーDOI: 10.2210/pdb7bgm/pdb
• 分子名称: Phosphoribosyl-AMP cyclohydrolase, ZINC ION (3 entities in total)
• 機能のキーワード: histidine, pyrophosphohydrolase, cyclohydrolase, bifunctional, pra-ch, pra-ph, hydrolase
• 由来する生物種: Medicago truncatula (Barrel medic)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53972.81

構造登録者

Witek, W.,Ruszkowski, M. (登録日: 2021-01-08, 公開日: 2021-05-19, 最終更新日: 2024-05-15)

主引用文献

Witek, W.,Sliwiak, J.,Ruszkowski, M.
Structural and mechanistic insights into the bifunctional HISN2 enzyme catalyzing the second and third steps of histidine biosynthesis in plants.
Sci Rep, 11:9647-9647, 2021

PubMed Abstract: The second and third steps of the histidine biosynthetic pathway (HBP) in plants are catalyzed by a bifunctional enzyme-HISN2. The enzyme consists of two distinct domains, active respectively as a phosphoribosyl-AMP cyclohydrolase (PRA-CH) and phosphoribosyl-ATP pyrophosphatase (PRA-PH). The domains are analogous to single-domain enzymes encoded by bacterial hisI and hisE genes, respectively. The calculated sequence similarity networks between HISN2 analogs from prokaryotes and eukaryotes suggest that the plant enzymes are closest relatives of those in the class of Deltaproteobacteria. In this work, we obtained crystal structures of HISN2 enzyme from Medicago truncatula (MtHISN2) and described its architecture and interactions with AMP. The AMP molecule bound to the PRA-PH domain shows positioning of the N1-phosphoribosyl relevant to catalysis. AMP bound to the PRA-CH domain mimics a part of the substrate, giving insights into the reaction mechanism. The latter interaction also arises as a possible second-tier regulatory mechanism of the HBP flux, as indicated by inhibition assays and isothermal titration calorimetry.

PubMed: 33958623
DOI: 10.1038/s41598-021-88920-2

実験手法

X-RAY DIFFRACTION (1.6 Å)