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The refined 2.3 Å crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor
Author(s) -
An-Zhi Wei,
Mayr Irmgard,
Bode Wolfram
Publication year - 1988
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(88)80118-2
Subject(s) - chemistry , ketone , stereochemistry , covalent bond , valine , elastase , pancreatic elastase , enzyme , crystal structure , crystallography , amino acid , biochemistry , organic chemistry
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 Å). 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 α‐carbon atoms is 0.32 Å. 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.