5CDZ

Crystal structure of conserpin in the latent state

5CDZ の概要

• エントリーDOI: 10.2210/pdb5cdz/pdb
• 関連するPDBエントリー: 5CDX 5CE0 5CE2
• 分子名称: Conserpin in the latent state, GLYCEROL (3 entities in total)
• 機能のキーワード: serine protease inhibitor, aggregation resistant, consensus design, stability, latent state, hydrolase, hydrolase inhibitor
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42762.52

構造登録者

Porebski, B.T.,McGowan, S.,Keleher, S.,Buckle, A.M. (登録日: 2015-07-06, 公開日: 2016-07-20, 最終更新日: 2023-09-27)

主引用文献

Porebski, B.T.,Keleher, S.,Hollins, J.J.,Nickson, A.A.,Marijanovic, E.M.,Borg, N.A.,Costa, M.G.,Pearce, M.A.,Dai, W.,Zhu, L.,Irving, J.A.,Hoke, D.E.,Kass, I.,Whisstock, J.C.,Bottomley, S.P.,Webb, G.I.,McGowan, S.,Buckle, A.M.
Smoothing a rugged protein folding landscape by sequence-based redesign.
Sci Rep, 6:33958-33958, 2016

PubMed Abstract: The rugged folding landscapes of functional proteins puts them at risk of misfolding and aggregation. Serine protease inhibitors, or serpins, are paradigms for this delicate balance between function and misfolding. Serpins exist in a metastable state that undergoes a major conformational change in order to inhibit proteases. However, conformational labiality of the native serpin fold renders them susceptible to misfolding, which underlies misfolding diseases such as α-antitrypsin deficiency. To investigate how serpins balance function and folding, we used consensus design to create conserpin, a synthetic serpin that folds reversibly, is functional, thermostable, and polymerization resistant. Characterization of its structure, folding and dynamics suggest that consensus design has remodeled the folding landscape to reconcile competing requirements for stability and function. This approach may offer general benefits for engineering functional proteins that have risky folding landscapes, including the removal of aggregation-prone intermediates, and modifying scaffolds for use as protein therapeutics.

PubMed: 27667094
DOI: 10.1038/srep33958

実験手法

X-RAY DIFFRACTION (1.449 Å)