4WYN

The crystal structure of the A109G mutant of RNase A

4WYN の概要

• エントリーDOI: 10.2210/pdb4wyn/pdb
• 分子名称: Ribonuclease pancreatic (2 entities in total)
• 機能のキーワード: conformational dynamics, hydrolase
• 由来する生物種: Bos taurus (Bovine)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27650.99

構造登録者

French, R.L.,Gagne, D.,Doucet, N.,Simonovic, M. (登録日: 2014-11-17, 公開日: 2015-11-18, 最終更新日: 2024-10-23)

主引用文献

Gagne, D.,French, R.L.,Narayanan, C.,Simonovic, M.,Agarwal, P.K.,Doucet, N.
Perturbation of the Conformational Dynamics of an Active-Site Loop Alters Enzyme Activity.
Structure, 23:2256-2266, 2015

PubMed Abstract: The role of internal dynamics in enzyme function is highly debated. Specifically, how small changes in structure far away from the reaction site alter protein dynamics and overall enzyme mechanisms is of wide interest in protein engineering. Using RNase A as a model, we demonstrate that elimination of a single methyl group located >10 Å away from the reaction site significantly alters conformational integrity and binding properties of the enzyme. This A109G mutation does not perturb structure or thermodynamic stability, both in the apo and ligand-bound states. However, significant enhancement in conformational dynamics was observed for the bound variant, as probed over nano- to millisecond timescales, resulting in major ligand repositioning. These results illustrate the large effects caused by small changes in structure on long-range conformational dynamics and ligand specificities within proteins, further supporting the importance of preserving wild-type dynamics in enzyme systems that rely on flexibility for function.

PubMed: 26655472
DOI: 10.1016/j.str.2015.10.011

実験手法

X-RAY DIFFRACTION (1.805 Å)