3f02 | pdb_00003f02

Cleaved human neuroserpin

spinqualitylabelsall models 3f02, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3f02 is a 4 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 1.8Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease NEUS_HUMAN Familial encephalopathy with neuroserpin inclusion bodies. The disease is caused by mutations affecting the gene represented in this entry. Function NEUS_HUMAN Serine protease inhibitor that inhibits plasminogen activators and plasmin but not thrombin. May be involved in the formation or reorganization of synaptic connections as well as for synaptic plasticity in the adult nervous system. May protect neurons from cell damage by tissue-type plasminogen activator. 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 Human neuroserpin (hNS) is a protein serine protease inhibitor expressed mainly in the nervous system, where it plays key roles in neural development and plasticity by primarily targeting tissue plasminogen activator (tPA). Four hNS mutations are associated to a form of autosomal dominant dementia, known as familial encephalopathy with neuroserpin inclusion bodies. The medical interest in and the lack of structural information on hNS prompted us to study the crystal structure of native and cleaved hNS, reported here at 3.15 and 1.85 A resolution, respectively. In the light of the three-dimensional structures, we focus on the hNS reactive centre loop in its intact and cleaved conformations relative to the current serpin polymerization models and discuss the protein sites hosting neurodegenerative mutations. On the basis of homologous serpin structures, we suggest the location of a protein surface site that may stabilize the hNS native (metastable) form. In parallel, we present the results of kinetic studies on hNS inhibition of tPA. Our data analysis stresses the instability of the hNS-tPA complex with a dissociation half-life of minutes compared to a half-life of weeks observed for other serpin-cognate protease complexes. Human neuroserpin: structure and time-dependent inhibition.,Ricagno S, Caccia S, Sorrentino G, Antonini G, Bolognesi M J Mol Biol. 2009 Apr 24;388(1):109-21. Epub 2009 Mar 2. PMID:19265707 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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