4PCN

Phosphotriesterase variant R22

4PCN の概要

• エントリーDOI: 10.2210/pdb4pcn/pdb
• 関連するPDBエントリー: 4PBE 4PBF 4PCP 4XAF 4XAG 4XAY 4XAZ 4XD3 4XD4 4XD5 4XD6
• 分子名称: Phosphotriesterase variant PTE-R22, (4S)-2-METHYL-2,4-PENTANEDIOL, ZINC ION, ... (4 entities in total)
• 機能のキーワード: phosphotriesterase, arylesterase, evolution, hydrolase
• 由来する生物種: Brevundimonas diminuta
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73291.29

構造登録者

Jackson, C.J.,Campbell, E.,Kaltenbach, M.,Tokuriki, N. (登録日: 2014-04-16, 公開日: 2015-05-06, 最終更新日: 2023-11-15)

主引用文献

Campbell, E.,Kaltenbach, M.,Correy, G.J.,Carr, P.D.,Porebski, B.T.,Livingstone, E.K.,Afriat-Jurnou, L.,Buckle, A.M.,Weik, M.,Hollfelder, F.,Tokuriki, N.,Jackson, C.J.
The role of protein dynamics in the evolution of new enzyme function.
Nat. Chem. Biol., 12:944-950, 2016

PubMed Abstract: Enzymes must be ordered to allow the stabilization of transition states by their active sites, yet dynamic enough to adopt alternative conformations suited to other steps in their catalytic cycles. The biophysical principles that determine how specific protein dynamics evolve and how remote mutations affect catalytic activity are poorly understood. Here we examine a 'molecular fossil record' that was recently obtained during the laboratory evolution of a phosphotriesterase from Pseudomonas diminuta to an arylesterase. Analysis of the structures and dynamics of nine protein variants along this trajectory, and three rationally designed variants, reveals cycles of structural destabilization and repair, evolutionary pressure to 'freeze out' unproductive motions and sampling of distinct conformations with specific catalytic properties in bi-functional intermediates. This work establishes that changes to the conformational landscapes of proteins are an essential aspect of molecular evolution and that change in function can be achieved through enrichment of preexisting conformational sub-states.

PubMed: 27618189
DOI: 10.1038/nchembio.2175

実験手法

X-RAY DIFFRACTION (1.54 Å)