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Title
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The refined 2.3 A crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor.
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Authors
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A.Z.Wei,
I.Mayr,
W.Bode.
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Ref.
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FEBS Lett, 1988,
234,
367-373.
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PubMed id
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Abstract
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The stoichiometric complex formed between human leukocyte elastase and a
synthetic MeO-Suc-Ala-Ala-Pro-Val chloromethyl ketone inhibitor was
co-crystallized and its X-ray structure determined, using Patterson search
methods. Its structure has been crystallographically refined to a final R value
of 0.145 (8.0 and 2.3 A). The enzyme structure is very similar to that recently
observed in a complex formed with the ovomucoid third domain from turkey [(1986)
EMBO J. 5,2453-2458]. The rms deviation of all alpha-carbon atoms is 0.32 A. The
peptidic inhibitor is bound in a similar overall conformation as the ovomucoid
binding segment. Covalent bonds are formed between Val-P1 of the inhibitor and
His-57 NE2 and Ser-195 OG of the enzyme. The carbonyl carbon is tetrahedrally
deformed to a hemiketal. The valine side chain is arranged in the S1 pocket in
the g-conformation.
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