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Title
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The active site of aspartic proteinases.
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Authors
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L.Pearl,
T.Blundell.
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Ref.
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Febs Lett, 1984,
174,
96.
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PubMed id
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Abstract
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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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