The active site of aspartic proteinases |
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Authors: | L Pearl T Blundell |
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Affiliation: | Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet Street, London WC1E 7HX, England |
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Abstract: | The active site of the aspartic proteinase, endothiapepsin, has been defined by X-ray analysis and restrained least-squares refinement at 2.1 A resolution with a crystallographic agreement value of 0.16. The environments of the two catalytically important aspartyl groups are remarkably similar and the contributions of the NH2- and COOH-terminal domains to the catalytic centre are related by a local 2-fold axis. The carboxylates of the aspartyls share a hydrogen bond and have equivalent contacts to a bound water molecule or hydroxonium ion lying on the local diad. The main chains around 32 and 215 are connected by a novel interaction involving diad-related threonines. It is suggested that the two pKa values of the active site aspartyls arise from a structure not unlike that in maleic acid with a hydrogen-bonded intermediate species and a dicarboxylate characterised by electrostatic repulsions between the two negatively charged groups. |
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Keywords: | Active site Enzyme conformation Protein crystallography Aspartic proteinase Catalytic mechanism X-ray analysis |
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