2et2

Crystal structure of an Asn to Ala mutant of Winged Bean Chymotrypsin Inhibitor protein

spinqualitylabelsall models 2et2, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2et2 is a 1 chain structure with sequence from Psophocarpus tetragonolobus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: NI, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ICW3_PSOTE Inhibits alpha-chymotrypsin at the molar ratio of 1:2 in state of 1:1. 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 The scaffold of serine protease inhibitors plays a significant role in the process of religation which resists proteolysis of the inhibitor in comparison to a substrate. Although the role of the conserved scaffolding Asn residue was previously implicated in the maintenance of the binding loop conformation of Kunitz (STI) inhibitors, its possible involvement in the prevention of proteolysis is still unexplored. In this paper, we have investigated the specific role of the spacer Asn in the prevention of proteolysis through structural and biochemical studies on the mutants where Asn14 of winged bean chymotrypsin inhibitor (WCI) has been replaced by Gly, Ala, Thr, Leu, and Gln. A residue having no side chain or beta-branching at the 14th position creates deformation and insufficient protrusion of the binding loop, and as a result N14G and N14T lose the ability to recognize proteases. Although the reactive site loop conformation of N14A and N14Q are almost identical to WCI, biochemical results present N14A as a substrate indicating that the methyl group of Ala14 is not suitable to capture the cleaved parts together for religation. The poor inhibitory power of N14L points toward the chemical incompatibility of Leu at the 14th position, although its size is the same as Asn; on the other hand, slight loss of inhibitory potency of N14Q is attributed to the inappropriate placement of the Gln14 polar head, caused by the strained accommodation of its bigger side chain. These observations collectively allow us to conclude that the side chain of spacer Asn fits snugly into the concave space of the reactive site loop cavity and its ND2 atom forms hydrogen bonds with the P2 and P1' carbonyl O at either side of the scissile bond holding the cleaved products together for religation. Through database analysis, we have identified such spacer asparagines in five other families of serine protease inhibitors with a similar disposition of their ND2 atoms, which supports our proposition. Spacer Asn determines the fate of Kunitz (STI) inhibitors, as revealed by structural and biochemical studies on WCI mutants.,Dasgupta J, Khamrui S, Dattagupta JK, Sen U Biochemistry. 2006 Jun 6;45(22):6783-92. PMID:16734415 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Chymotrypsin inhibitor 3D structures

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