1bll

X-RAY CRYSTALLOGRAPHIC DETERMINATION OF THE STRUCTURE OF BOVINE LENS LEUCINE AMINOPEPTIDASE COMPLEXED WITH AMASTATIN: FORMULATION OF A CATALYTIC MECHANISM FEATURING A GEM-DIOLATE TRANSITION STATE

spinqualitylabelsall models 1bll, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1bll is a 2 chain structure with sequence from Bos taurus and Streptomyces sp. ME98-M3. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: ACE, L2O, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AMPL_BOVIN Presumably involved in the processing and regular turnover of intracellular proteins. Catalyzes the removal of unsubstituted N-terminal amino acids from various peptides. 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 structure of the complex of bovine lens leucine aminopeptidase (blLAP) with the slow-, tight-binding inhibitor amastatin has been determined by X-ray crystallography. X-ray diffraction data were collected at -150 degrees C from a single blLAP-amastatin crystal which under the data collection conditions was of the space group P6(3)22 with unit cell parameters a = 130.3 A and c = 121.9 A. The structure of the blLAP-amastatin complex was determined by molecular replacement, using the structure of native blLAP as the starting model. Refinement of the blLAP-amastatin model plus 132 water molecules against data from 10.0- to 2.4-A resolution resulted in a final structure with a crystallographic residual of 0.198. The binding mode of amastatin is similar to that of bestatin, the structure of whose complex with blLAP has previously been determined. Of particular note, the N-terminus-to-C-terminus orientation of the two bound inhibitors is the same. The two N-terminal residues of amastatin and bestatin occupy the same binding sites, which are most likely S1 and S'1. The slow binding of amastatin and bestatin may be partially attributable to a binding mechanism in which the two active site metals are sequentially coordinated by the P1 amino and hydroxyl groups of these inhibitors. A catalytic mechanism for blLAP is proposed based on the binding modes of amastatin and bestatin and plausible binding modes of a dipeptide substrate and its putative gem-diolate transition state which were modeled into the active site of blLAP after the binding mode of amastatin. The proposed catalytic mechanism invokes roles for the catalytic metals in binding and activating the substrate and in stabilizing the transition state. The mechanism also includes roles for Asp-255 as a general base, Arg-336 as an additional electrophilic substrate activator and transition state stabilizer, and Lys-262 as a proton shuttle. X-ray crystallographic determination of the structure of bovine lens leucine aminopeptidase complexed with amastatin: formulation of a catalytic mechanism featuring a gem-diolate transition state.,Kim H, Lipscomb WN Biochemistry. 1993 Aug 24;32(33):8465-78. PMID:8357796 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminopeptidase 3D structures

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