5CDX

Crystal structure of conserpin

Summary for 5CDX

• Entry DOI: 10.2210/pdb5cdx/pdb
• Related: 5CDZ 5CE0 5CE2
• Descriptor: Conserpin (2 entities in total)
• Functional Keywords: serine protease inhibitor, aggregation resistant, consensus design, stability, hydrolase inhibitor
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 42578.33

Authors

Porebski, B.T.,Borg, N.A.,McGowan, S.,Buckle, A.M. (deposition date: 2015-07-06, release date: 2016-07-20, Last modification date: 2023-09-27)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)