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Title
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Analogous inhibitors of elastase do not always bind analogously.
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Authors
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C.Mattos,
B.Rasmussen,
X.Ding,
G.A.Petsko,
D.Ringe.
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Ref.
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Nat Struct Biol, 1994,
1,
55-58.
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PubMed id
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Abstract
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It has been assumed that the structure of a single inhibitor complex is
sufficient to define the available subsites of an enzyme that has a unique
binding site and a uniquely defined mode for ligand binding--the specificity for
these subsites can thus be probed by kinetic experiments. Elastase is an enzyme
for which these traditional assumptions, which underlie such structural and
kinetic studies, do not hold. Three new crystal structures of elastase complexed
to chemically similar inhibitors with similar binding affinities reveal a
diversity of binding modes as well as two new subsites on elastase. The
existence of multiple binding sites and different binding modes for such similar
inhibitors indicates that researchers must proceed with caution when using
kinetics to map out protein subsites.
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