5du3 | pdb_00005du3

Active form of human C1-inhibitor

spinqualitylabelsall models 5du3, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5du3 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease IC1_HUMAN Defects in SERPING1 are the cause of hereditary angioedema (HAE) [MIM:106100; also called hereditary angioneurotic edema (HANE). HAE is an autosomal dominant disorder characterized by episodic local subcutaneous edema and submucosal edema involving the upper respiratory and gastrointestinal tracts. HAE due to C1 esterase inhibitor deficiency is comprised of two clinically indistinguishable forms. In HAE type 1, representing 85% of patients, serum levels of C1 esterase inhibitor are less than 35% of normal. In HAE type 2, the levels are normal or elevated, but the protein is non-functional. [:] Function IC1_HUMAN Activation of the C1 complex is under control of the C1-inhibitor. It forms a proteolytically inactive stoichiometric complex with the C1r or C1s proteases. May play a potentially crucial role in regulating important physiological pathways including complement activation, blood coagulation, fibrinolysis and the generation of kinins. Very efficient inhibitor of FXIIa. Inhibits chymotrypsin and kallikrein. Publication Abstract from PubMed C1-inhibitor is a key inhibitor of the complement and contact activation systems, and mutations in the protein can cause hereditary angioedema. Through an unknown mechanism, polysaccharides can increase C1-inhibitor activity against some of its target proteases. Here we present the crystal structures of the serine protease inhibitor (serpin) domain of active C1-inhibitor by itself and in complex with dextran sulfate. Unlike previously described interactions of serpins with polysaccharides, the structures and isothermal titration calorimetry experiments together reveal that dextran sulfate binds to C1-inhibitor's F1 helix with low affinity and does not invoke an allosteric change. Furthermore, one dextran sulfate molecule can bind multiple C1-inhibitor molecules. We propose that in a C1-inhibitor/protease/polysaccharide ternary complex, negatively charged polysaccharides link C1-inhibitor's positively charged F1 helix to positively charged autolysis loops of proteases. The proposed mechanism elegantly explains previous experiments showing that polysaccharide potentiation is increased against proteases with a greater positive charge in their autolysis loop. How Dextran Sulfate Affects C1-inhibitor Activity: A Model for Polysaccharide Potentiation.,Dijk M, Holkers J, Voskamp P, Giannetti BM, Waterreus WJ, van Veen HA, Pannu NS Structure. 2016 Dec 6;24(12):2182-2189. doi: 10.1016/j.str.2016.09.013. Epub 2016, Nov 3. PMID:27818099 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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