2zvx

Structure of a BPTI-[5,55] variant containing Gly/Val at the 14/38th positions

spinqualitylabelsall models 2zvx, resolution 1.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2zvx is a 2 chain structure with sequence from Bovin. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4 Related: 2zjx, 3ci7 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [BPT1_BOVIN] Inhibits trypsin, kallikrein, chymotrypsin, and plasmin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Enhancing protein conformational stability is an important aspect of protein engineering and biotechnology. However, protein stabilization is difficult to rationalize as it often results from the small cumulative and intertwined effects of multiple mutations. Here, we analyzed the mechanisms behind a remarkable 13 degrees stabilization produced by a single A14G and a double A14GA38V mutation in BPTI-[5,55], a natively folded bovine pancreatic trypsin inhibitor variant. Differential scanning calorimetry analysis of three BPTI-[5,55] variants (A14G, A38V, and A14GA38V) indicated that the A14G mutation stabilized the structure enthalpically, whereas the A38V stabilization was entropy driven. We also determined the structure of the A14GA38V mutant at 1.09 A resolution, whereas the A38V variant did not crystallize, and we previously reported the A14G variant's structure (2ZJX). The overall structures of the A14G and A14GA38V variants were very similar to that of wild-type BPTI, but small local structure perturbations around residues 14 and 38 strongly suggested potential factors contributing to the enthalpy stabilization. First, the A14G mutation displaced the local backbone structures around residues 14 and 38 by up to 0.7 A, presumably increasing local van der Waals interactions. Next, this displacement produced steric clashes between neighboring residue's side-chains in all but the variants containing the A14G mutation. Noteworthy, these clashes are not predicted from the wild type BPTI structure. These observations provide one of the first unambiguous analyses of how a subtle interplay between the sidechain and backbone structures can have a major effect on protein stability. Proteins 2009. (c) 2009 Wiley-Liss, Inc. Thermodynamic and structural analysis of highly stabilized BPTIs by single and double mutations.,Islam MM, Sohya S, Noguchi K, Kidokoro S, Yohda M, Kuroda Y Proteins. 2009 Dec;77(4):962-70. PMID:19830687 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Basic Pancreatic Trypsin Inhibitor

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