1ize

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Crystal structure of Aspergillus oryzae Aspartic proteinase complexed with pepstatin

File:1ize.jpg


1ize, resolution 1.90Å

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OverviewOverview

The X-ray structures of Aspergillus oryzae aspartic proteinase (AOAP) and, its complex with inhibitor pepstatin have been determined at 1.9A, resolution. AOAP was crystallized in an orthorhombic system with the space, group P2(1)2(1)2(1) and cell dimensions of a=49.4A, b=79.4A, and c=93.6A., By the soaking of pepstatin, crystals are transformed into a monoclinic, system with the space group C2 and cell dimensions of a=106.8A, b=38.6A, c=78.7A, and beta=120.3 degrees. The structures of AOAP and AOAP/pepstatin, complex were refined to an R-factor of 0.177 (R(free)=0.213) and of 0.185, (0.221), respectively. AOAP has a crescent-shaped structure with two lobes, (N-lobe and C-lobe) and the deep active site cleft is constructed between, them. At the center of the active site cleft, two Asp residues (Asp33 and, Asp214) form the active dyad with a hydrogen bonding solvent molecule, between them. Pepstatin binds to the active site cleft via hydrogen bonds, and hydrophobic interactions with the enzyme. The structures of AOAP and, AOAP/pepstatin complex including interactions between the enzyme and, pepstatin are very similar to those of other structure-solved aspartic, proteinases and their complexes with pepstatin. Generally, aspartic, proteinases cleave a peptide bond between hydrophobic amino acid residues, but AOAP can also recognize the Lys/Arg residue as well as hydrophobic, amino acid residues, leading to the activation of trypsinogen and, chymotrypsinogen. The X-ray structure of AOAP/pepstatin complex and, preliminary modeling show two possible sites of recognition for the, positively charged groups of Lys/Arg residues around the active site of, AOAP.

About this StructureAbout this Structure

1IZE is a Single protein structure of sequence from Aspergillus oryzae with MAN and IHN as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structures of Aspergillus oryzae aspartic proteinase and its complex with an inhibitor pepstatin at 1.9A resolution., Kamitori S, Ohtaki A, Ino H, Takeuchi M, J Mol Biol. 2003 Mar 7;326(5):1503-11. PMID:12595261

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