6X7H

Cyanovirin-N Mutation I34Y with Dimannose bound

6X7H の概要

• エントリーDOI: 10.2210/pdb6x7h/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900111
• 分子名称: Cyanovirin-N, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose (3 entities in total)
• 機能のキーワード: mannose binding protein antiviral protein, antiviral protein
• 由来する生物種: Nostoc ellipsosporum
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 24682.82

構造登録者

Fromme, R.,Sharma, P.,Ghirlanda, G. (登録日: 2020-05-30, 公開日: 2021-06-02, 最終更新日: 2023-10-25)

主引用文献

Kazan, I.C.,Sharma, P.,Rahman, M.I.,Bobkov, A.,Fromme, R.,Ghirlanda, G.,Ozkan, S.B.
Design of novel cyanovirin-N variants by modulation of binding dynamics through distal mutations.
Elife, 11:-, 2022

PubMed Abstract: We develop integrated co-evolution and dynamic coupling (ICDC) approach to identify, mutate, and assess distal sites to modulate function. We validate the approach first by analyzing the existing mutational fitness data of TEM-1 β-lactamase and show that allosteric positions co-evolved and dynamically coupled with the active site significantly modulate function. We further apply ICDC approach to identify positions and their mutations that can modulate binding affinity in a lectin, cyanovirin-N (CV-N), that selectively binds to dimannose, and predict binding energies of its variants through Adaptive BP-Dock. Computational and experimental analyses reveal that binding enhancing mutants identified by ICDC impact the dynamics of the binding pocket, and show that rigidification of the binding residues compensates for the entropic cost of binding. This work suggests a mechanism by which distal mutations modulate function through dynamic allostery and provides a blueprint to identify candidates for mutagenesis in order to optimize protein function.

PubMed: 36472898
DOI: 10.7554/eLife.67474

実験手法

X-RAY DIFFRACTION (1.25 Å)