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PDBsum entry 5est
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Hydrolase/hydrolase inhibitor
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PDB id
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5est
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystallographic analysis of the inhibition of porcine pancreatic elastase by a peptidyl boronic acid: structure of a reaction intermediate.
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Authors
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L.H.Takahashi,
R.Radhakrishnan,
R.E.Rosenfield,
E.F.Meyer.
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Ref.
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Biochemistry, 1989,
28,
7610-7617.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structure of porcine pancreatic elastase (PPE) complexed to
carbobenzoxy-alanylisoleucine-boronic acid (ZAIB) is reported to 2.09-A
resolution and refined to an R factor of 0.15. This is the first reported
structural analysis of PPE with an isoleucine residu in the primary specificity
pocket. The results include (1) marked displacement of the inhibitor out of the
active site leading to (2) a close (2.2 A) direct contact between B (boron atom
of the inhibitor) and N epsilon of His-57 and also (3) covalent bonding (1.5 A)
to O gamma of Ser-195. A scheme for the mechanism of inhibition of PPE by ZAIB
is proposed. A comparison with a peptidyl difluoromethyl ketone-PPE complex (Ki
= 9.5 microns) is made to explain the strong inhibition of PPE by ZAIB (Ki = 0.3
micron). These results lead us to characterize this structure as a time- and
space-averaged reaction intermediate, providing fresh insight into the cramped
dimensions available in enzymatic catalyses.
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Secondary reference #1
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Title
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Structure of native porcine pancreatic elastase at 1.65 a resolutions.
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Authors
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E.Meyer,
G.Cole,
R.Radhakrishnan,
O.Epp.
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Ref.
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Acta Crystallogr B, 1988,
44,
26-38.
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PubMed id
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