6GDD

DIHYDROOROTASE FROM AQUIFEX AEOLICUS UNDER 1200 BAR OF HYDROSTATIC PRESSURE

6GDD の概要

• エントリーDOI: 10.2210/pdb6gdd/pdb
• 関連するPDBエントリー: 1XRF 1XRT
• 分子名称: Dihydroorotase, ZINC ION, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: dihydroorotase, aquifex aeolicus, hydrostatic pressure, room temperature, hydrolase
• 由来する生物種: Aquifex aeolicus (strain VF5)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46602.19

構造登録者

Prange, T.,Girard, E.,Herve, G.,Evans, D.R. (登録日: 2018-04-23, 公開日: 2019-01-30, 最終更新日: 2024-01-17)

主引用文献

Prange, T.,Girard, E.,Fourme, R.,Dhaussy, A.C.,Edwards, B.,Vaishnav, A.,Patel, C.,Guy-Evans, H.,Herve, G.,Evans, D.R.
Pressure-induced activation of latent dihydroorotase from Aquifex aeolicus as revealed by high pressure protein crystallography.
Febs J., 286:1204-1213, 2019

PubMed Abstract: Dihydroorotase (DHOase) is involved in the de novo synthesis of pyrimidine in virtually all organisms, and it is usually associated with two other enzymes found in this biosynthetic pathway, carbamylphosphate synthetase and/or aspartate transcarbamylase (ATCase). In the hyperthermophilic bacterium Aquifex aeolicus, ATCase and DHOase are noncovalently associated. Upon dissociation, ATCase keeps its activity entirely while DHOase is totally inactivated. It was previously shown that high pressure fully restores the activity of this isolated DHOase. On the basis of kinetic studies, site-directed mutagenesis and the use of peptides mimicking loop A, a loop that appears to block access to the active site, was proposed that this pressure-induced reactivation was due to the decrease in the volume of the system, -ΔV, resulting from the disruption of known ionic interactions between the loop and the main part of the protein. In this study, this interpretation is more precisely demonstrated by the determination of the crystallographic structure of isolated DHOase under pressure. In addition to the loop displacements, pressure induces a discrete rearrangement of the catalytic site aspartate 305, an effect that might additionally contribute to the reactivation of this enzyme.

PubMed: 30657257
DOI: 10.1111/febs.14758

実験手法

X-RAY DIFFRACTION (2.6 Å)