6A35

Crystal structure of 5-methylthioribose 1-phosphate isomerase from Pyrococcus horikoshii OT3 - Form II

6A35 の概要

• エントリーDOI: 10.2210/pdb6a35/pdb
• 分子名称: Putative methylthioribose-1-phosphate isomerase (2 entities in total)
• 機能のキーワード: methionine salvage pathway, ph0702, cis-phosphoenolate intermediate, hydride transfer, isomerase
• 由来する生物種: Pyrococcus horikoshii OT3
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 161729.92

構造登録者

Kanaujia, S.P.,Gogoi, P.,Mordina, P. (登録日: 2018-06-14, 公開日: 2018-12-12, 最終更新日: 2024-10-30)

主引用文献

Gogoi, P.,Mordina, P.,Kanaujia, S.P.
Structural insights into the catalytic mechanism of 5-methylthioribose 1-phosphate isomerase.
J. Struct. Biol., 205:67-77, 2019

PubMed Abstract: 5-Methylthioribose 1-phosphate isomerase (M1Pi) is a crucial enzyme involved in the universally conserved methionine salvage pathway (MSP) where it is known to catalyze the conversion of 5-methylthioribose 1-phosphate (MTR-1-P) to 5-methylthioribulose 1-phosphate (MTRu-1-P) via a mechanism which remains unspecified till date. Furthermore, although M1Pi has a discrete function, it surprisingly shares high structural similarity with two functionally non-related proteins such as ribose-1,5-bisphosphate isomerase (R15Pi) and the regulatory subunits of eukaryotic translation initiation factor 2B (eIF2B). To identify the distinct structural features that lead to divergent functional obligations of M1Pi as well as to understand the mechanism of enzyme catalysis, the crystal structure of M1Pi from a hyperthermophilic archaeon Pyrococcus horikoshii OT3 was determined. A meticulous structural investigation of the dimeric M1Pi revealed the presence of an N-terminal extension and a hydrophobic patch absent in R15Pi and the regulatory α-subunit of eIF2B. Furthermore, unlike R15Pi in which a kink formation is observed in one of the helices, the domain movement of M1Pi is distinguished by a forward shift in a loop covering the active-site pocket. All these structural attributes contribute towards a hydrophobic microenvironment in the vicinity of the active site of the enzyme making it favorable for the reaction mechanism to commence. Thus, a hydrophobic active-site microenvironment in addition to the availability of optimal amino-acid residues surrounding the catalytic residues in M1Pi led us to propose its probable reaction mechanism via a cis-phosphoenolate intermediate formation.

PubMed: 30471343
DOI: 10.1016/j.jsb.2018.11.007

実験手法

X-RAY DIFFRACTION (2.65 Å)