4bd9

Structure of the complex between SmCI and human carboxypeptidase A4

spinqualitylabelsall models 4bd9, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bd9 is a 2 chain structure with sequence from Homo sapiens and Sabellastarte magnifica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN Related: 2bo9, 2boa, 4a94 Resources: FirstGlance, OCA, RCSB, PDBsum Function [CBPA4_HUMAN] Metalloprotease that could be involved in the histone hyperacetylation pathway. Publication Abstract from PubMed The crystal structure of SmCI (Sabellastarte magnifica carboxypeptidase inhibitor) has been determined in complex with human carboxypeptidase A4 (hCPA4). SmCI is composed by three BPTI/Kunitz domains, each one displaying high structural homology and functionality with serine protease inhibitors. Moreover, SmCI possesses a distinctive capability to inhibit metallo-carboxypeptidases, constituting a bifunctional metallocarboxy- and serine protease inhibitor. The structure of the 1:1 complex of SmCI with hCPA4 reveals a noncanonical mechanism of carboxypeptidase inhibition, which surprisingly occurs mainly via the N-terminal segment, which penetrates into the active site groove of the enzyme. Mutagenesis and biochemical analysis confirm the major role of the N-terminal segment in the inhibition of carboxypeptidases. SmCI represents a tri-Kunitz serine protease inhibitor adapted to inhibit metallo-carboxypeptidases and discloses an unusual mechanism of inhibition by the N-terminal segment, emulating the "classical" C-terminal substrate-like inhibition. A Noncanonical Mechanism of Carboxypeptidase Inhibition Revealed by the Crystal Structure of the Tri-Kunitz SmCI in Complex with Human CPA4.,Alonso Del Rivero M, Reytor ML, Trejo SA, Chavez MA, Aviles FX, Reverter D Structure. 2013 Jul 2;21(7):1118-26. doi: 10.1016/j.str.2013.04.021. Epub 2013, Jun 6. PMID:23746805 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Carboxypeptidase

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