2MVZ

Solution Structure for Cyclophilin A from Geobacillus Kaustophilus

2MVZ の概要

• エントリーDOI: 10.2210/pdb2mvz/pdb
• NMR情報: BMRB: 18628
• 分子名称: Peptidyl-prolyl cis-trans isomerase (1 entity in total)
• 機能のキーワード: cyclophilin, thermophile, ppiase, isomerase
• 由来する生物種: Geobacillus kaustophilus (firmicutes)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16136.17

構造登録者

Holliday, M.J.,Isern, N.G.,Geoffrey, A.S.,Zhang, F.,Eisenmesser, E.Z. (登録日: 2014-10-20, 公開日: 2015-07-08, 最終更新日: 2024-05-01)

主引用文献

Holliday, M.J.,Camilloni, C.,Armstrong, G.S.,Isern, N.G.,Zhang, F.,Vendruscolo, M.,Eisenmesser, E.Z.
Structure and Dynamics of GeoCyp: A Thermophilic Cyclophilin with a Novel Substrate Binding Mechanism That Functions Efficiently at Low Temperatures.
Biochemistry, 54:3207-3217, 2015

PubMed Abstract: Thermophilic proteins have found extensive use in research and industrial applications because of their high stability and functionality at elevated temperatures while simultaneously providing valuable insight into our understanding of protein folding, stability, dynamics, and function. Cyclophilins, constituting a ubiquitously expressed family of peptidyl-prolyl isomerases with a range of biological functions and disease associations, have been utilized both for conferring stress tolerances and in exploring the link between conformational dynamics and enzymatic function. To date, however, no active thermophilic cyclophilin has been fully biophysically characterized. Here, we determine the structure of a thermophilic cyclophilin (GeoCyp) from Geobacillus kaustophilus, characterize its dynamic motions over several time scales using an array of methodologies that include chemical shift-based methods and relaxation experiments over a range of temperatures, and measure catalytic activity over a range of temperatures to compare its structure, dynamics, and function to those of a mesophilic counterpart, human cyclophilin A (CypA). Unlike those of most thermophile/mesophile pairs, GeoCyp catalysis is not substantially impaired at low temperatures as compared to that of CypA, retaining ~70% of the activity of its mesophilic counterpart. Examination of substrate-bound ensembles reveals a mechanism by which the two cyclophilins may have adapted to their environments through altering dynamic loop motions and a critical residue that acts as a clamp to regulate substrate binding differentially in CypA and GeoCyp. Fast time scale (pico- to nanosecond) dynamics are largely conserved between the two proteins, in accordance with the high degree of structural similarity, although differences do exist in their temperature dependencies. Slower (microsecond) time scale motions are likewise localized to similar regions in the two proteins with some variability in their magnitudes yet do not exhibit significant temperature dependencies in either enzyme.

PubMed: 25923019
DOI: 10.1021/acs.biochem.5b00263

実験手法

SOLUTION NMR