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PDBsum entry 1btw
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Hydrolase/hydrolase inhibitor
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PDB id
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1btw
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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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Episelection: novel ki approximately nanomolar inhibitors of serine proteases selected by binding or chemistry on an enzyme surface.
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Authors
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B.A.Katz,
J.Finer-Moore,
R.Mortezaei,
D.H.Rich,
R.M.Stroud.
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Ref.
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Biochemistry, 1995,
34,
8264-8280.
[DOI no: ]
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PubMed id
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Abstract
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A novel class of mechanism-based inhibitors of the serine proteases is developed
using epitaxial selection. Tripeptide boronates esterified by an alcohol or
alcohols at the boron retain the tight binding to trypsin-like enzymes
associated with transition-state analogs and incorporate additional groups that
can be utilized for selectivity between proteases. Formed by reaction of a
series of alcohols with the inhibitor boronate oxygen(s), the most structurally
compatible alcohol-derivatized inhibitors are either selected by binding to the
enzyme (epitaxial selection) or assembled by epitaxial reaction on the enzyme
surface. Mass spectrometry of the derivatized boronates and X-ray
crystallography of the complexes identify the chemical structures and the
three-dimensional interactions of inhibitors generated. This scheme also
engineers novel, potent (Ki approximately 7 nM), and more specific inhibitors of
individual serine proteases, by derivitizations of compounds obtained by
epitaxial selection.
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Secondary reference #1
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Title
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Solvent structure in crystals of trypsin determined by X-Ray and neutron diffraction.
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Authors
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J.S.Finer-Moore,
A.A.Kossiakoff,
J.H.Hurley,
T.Earnest,
R.M.Stroud.
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Ref.
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Proteins, 1992,
12,
203-222.
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PubMed id
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Secondary reference #2
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Title
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1.59 a structure of trypsin at 120 k: comparison of low temperature and room temperature structures.
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Authors
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T.Earnest,
E.Fauman,
C.S.Craik,
R.Stroud.
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Ref.
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Proteins, 1991,
10,
171-187.
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PubMed id
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Secondary reference #3
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Title
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Difference fourier refinement of the structure of dip-Trypsin at 1.5 angstroms using a minicomputer technique
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Authors
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J.L.Chambers,
R.M.Stroud.
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Ref.
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acta crystallogr ,sect b, 1977,
33,
1824.
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Secondary reference #4
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Title
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Structure and specific binding of trypsin: comparison of inhibited derivatives and a model for substrate binding.
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Authors
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M.Krieger,
L.M.Kay,
R.M.Stroud.
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Ref.
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J Mol Biol, 1974,
83,
209-230.
[DOI no: ]
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PubMed id
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Figure 1.
FIG. 1. Chemical structures: (I) benzamidina; (II) diisopropyl fluorophosphate; (III) N-ctaetyl
amino acid ethyl esters, (a) acetyl glycine ethyl ester, (b) acetyl lyine ethyl ester, (c) aoetl
arginine ethyl ester; (IV) ethyl p-midino benzoate; (V) ethyl p-amidino phenyl acetate.
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Figure 8.
FIG. 8. Electron density for His57 in the DIP-trpsin Fourier map, Gomputed for the plane
parallel to the imidazole ring.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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Secondary reference #5
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Title
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The crystal and molecular structure of dip-Inhibited bovine trypsin at2.7angstrom resolution.
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Authors
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R.M.Stroud,
L.M.Kay,
R.E.Dickerson.
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Ref.
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Cold Spring Harb Symp Quant Biol, 1972,
36,
125-140.
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PubMed id
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