5cdx | pdb_00005cdx

Crystal structure of conserpin

spinqualitylabelsall models 5cdx, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5cdx is a 1 chain structure with sequence from Synthetic construct sequences. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 5cdz, 5ce0, 5ce2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 alpha1-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. Smoothing a rugged protein folding landscape by sequence-based redesign.,Porebski BT, Keleher S, Hollins JJ, Nickson AA, Marijanovic EM, Borg NA, Costa MG, Pearce MA, Dai W, Zhu L, Irving JA, Hoke DE, Kass I, Whisstock JC, Bottomley SP, Webb GI, McGowan S, Buckle AM Sci Rep. 2016 Sep 26;6:33958. doi: 10.1038/srep33958. PMID:27667094 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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