4if8 | pdb_00004if8

Structure Of Vaspin

spinqualitylabelsall models 4if8, resolution 2.08Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4if8 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. Ligands: SO4 Gene: SERPINA12 (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Function [SPA12_HUMAN] May modulate insulin action conceivably only in the presence of its yet undefined target proteases in white adipose tissues. Publication Abstract from PubMed The molecular target of the adipokine vaspin (visceral adipose tissue-derived serpin; serpinA12) and its mode of action are unknown. Here, we provide the vaspin crystal structure and identify human kallikrein 7 (hK7) as a first protease target of vaspin inhibited by classical serpin mechanism with high specificity in vitro. We detect vaspin-hK7 complexes in human plasma and find co-expression of both proteins in murine pancreatic beta-cells. We further demonstrate that hK7 cleaves human insulin in the A- and B-chain. Vaspin treatment of isolated pancreatic islets leads to increased insulin concentration in the media upon glucose stimulation without influencing insulin secretion. By application of vaspin and generated inactive mutants, we find the significantly improved glucose tolerance in C57BL/6NTac and db/db mice treated with recombinant vaspin fully dependent on the vaspin serpin activity and not related to vaspin-mediated changes in insulin sensitivity as determined by euglycemic-hyperinsulinemic clamp studies. Improved glucose metabolism could be mediated by increased insulin plasma concentrations 150 min after a glucose challenge in db/db mice, supporting the hypothesis that vaspin may inhibit insulin degradation by hK7 in the circulation. In conclusion, we demonstrate the inhibitory serpin nature and the first protease target of the adipose tissue-derived serpin vaspin, and our findings suggest hK7 inhibition by vaspin as an underlying physiological mechanism for its compensatory actions on obesity-induced insulin resistance. Vaspin inhibits kallikrein 7 by serpin mechanism.,Heiker JT, Kloting N, Kovacs P, Kuettner EB, Strater N, Schultz S, Kern M, Stumvoll M, Bluher M, Beck-Sickinger AG Cell Mol Life Sci. 2013 Jan 31. PMID:23370777 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serpin

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