6CAN

Prolyl oligopeptidase mutant S477C from Pyrococcus furiosus

6CAN の概要

• エントリーDOI: 10.2210/pdb6can/pdb
• 関連するPDBエントリー: 5T88
• 分子名称: Prolyl endopeptidase, CHLORIDE ION (3 entities in total)
• 機能のキーワード: prolyl oligopeptidase, hyperthermostable, alpha/beta hydrolase, peptidase, hydrolase
• 由来する生物種: Pyrococcus furiosus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 142086.94

構造登録者

Ellis-Guardiola, K.,Lewis, J.C.,Sukumar, N. (登録日: 2018-01-31, 公開日: 2019-02-06, 最終更新日: 2023-10-04)

主引用文献

Ellis-Guardiola, K.,Rui, H.,Beckner, R.L.,Srivastava, P.,Sukumar, N.,Roux, B.,Lewis, J.C.
Crystal Structure and Conformational Dynamics of Pyrococcus furiosus Prolyl Oligopeptidase.
Biochemistry, 58:1616-1626, 2019

PubMed Abstract: Enzymes in the prolyl oligopeptidase family possess unique structures and substrate specificities that are important for their biological activity and for potential biocatalytic applications. The crystal structures of Pyrococcus furiosus ( Pfu) prolyl oligopeptidase (POP) and the corresponding S477C mutant were determined to 1.9 and 2.2 Å resolution, respectively. The wild type enzyme crystallized in an open conformation, indicating that this state is readily accessible, and it contained bound chloride ions and a prolylproline ligand. These structures were used as starting points for molecular dynamics simulations of Pfu POP conformational dynamics. The simulations showed that large-scale domain opening and closing occurred spontaneously, providing facile substrate access to the active site. Movement of the loop containing the catalytically essential histidine into a conformation similar to those found in structures with fully formed catalytic triads also occurred. This movement was modulated by chloride binding, providing a rationale for experimentally observed activation of POP peptidase catalysis by chloride. Thus, the structures and simulations reported in this study, combined with existing biochemical data, provide a number of insights into POP catalysis.

PubMed: 30786206
DOI: 10.1021/acs.biochem.9b00031

実験手法

X-RAY DIFFRACTION (2.2 Å)