The refined 2.3 A crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor.
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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Max-Planck-Institut für Biochemie, Martinsried, FRG.
Mayr
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Bode
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D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008958:Models, Molecular; D010196:Pancreatic Elastase / Q000097:blood*; D011485:Protein Binding; D011487:Protein Conformation; D014961:X-Ray Diffraction
D000590:Amino Acid Chloromethyl Ketones; C026704:methoxysuccinyl-alanyl-alanyl-prolyl-valine chloromethyl ketone; D010196:Pancreatic Elastase