2id4 | pdb_00002id4

The 1.9 A structure of Kex2 in complex with an Ac-R-E-R-K-chloromethyl ketone inhibitor.

spinqualitylabelsall models 2id4, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2id4 is a 4 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: 0QE, ACE, CA, CSO, LYK, MLA, NA, NAG, NDG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KEX2_YEAST Processing of precursors of alpha-factors and killer toxin. 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 high-resolution crystal structure of kexin (Kex2) in complex with a peptidyl-chloromethylketone inhibitor containing a noncognate lysine at the P(1) position provides the structural basis for the differential lysine/arginine selectivity that defines the prohormone (proprotein) convertase (PC) family. By comparison with the previous structures of Kex2 and furin, this structure of the acylated enzyme provides a basis for the observed decrease in the acylation rate with substrates containing a lysine at P(1) and the absence of an effect on the deacylation rate without involving mobility of the S(1) lid. The structure of the complex shows that a secondary subsite in the S(1) pocket is present, and that this site recognizes and binds the P(1) lysine in a more shallow fashion than arginine. This results in a displacement of the bound peptide away from the S385 nucleophile relative to substrates containing a P(1) arginine. It is concluded that this alternate binding site and resultant displacement of the scissile bond in the active site results in the observed decrease in the acylation rate. Studies of the inactivation kinetics of Kex2 by two peptidyl chloromethylketone inhibitors demonstrates that the selectivity between lysine and arginine at the P(1) position arises at the acylation step, consistent with what was observed with peptidyl substrates [Rockwell NC, Fuller RS (2001) J Biol Chem 276:38394-38399]. Differential P1 arginine and lysine recognition in the prototypical proprotein convertase Kex2.,Wheatley JL, Holyoak T Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6626-31. Epub 2007 Apr 10. PMID:17426142 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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