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Title
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X-ray diffraction analysis of the inhibition of porcine pancreatic elastase by a peptidyl trifluoromethylketone.
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Authors
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L.H.Takahashi,
R.Radhakrishnan,
R.E.Rosenfield,
E.F.Meyer,
D.A.Trainor,
M.Stein.
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Ref.
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J Mol Biol, 1988,
201,
423-428.
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PubMed id
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Abstract
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X-ray crystallographic data to 2.57 A resolution (1 A = 0.1 nm) have been
measured for the complex of a peptidyl trifluoromethylketone inhibitor with
porcine pancreatic elastase (PPE); R = 0.14. The inhibitor forms a stable
complex with the enzyme by means of a covalent attachment to active site Ser195O
gamma, resulting in a hemiketal moiety with tetrahedral geometry. The tripeptide
protion binds as an antiparallel beta-sheet, with four hydrogen bonds augmenting
the active-site covalent linkage, Ki = 9.5 microM. His57 exhibits a bifurcated
H-bond to both Ser195O gamma and an F atom of the inhibitor. This study is one
of a series which explores the binding geometry of a variety of small substrates
and inhibitors to PPE. This peptidyl-PPE complex affords insight into the
binding geometry of a novel trifluoromethylketone moiety to a serine proteinase.
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