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PDBsum entry 6est
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Hydrolase(serine proteinase)
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PDB id
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6est
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.21.36
- pancreatic elastase.
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Reaction:
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Hydrolysis of proteins, including elastin. Preferential cleavage: Ala-|-Xaa.
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J Mol Recognit
3:36-44
(1990)
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PubMed id:
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Interaction of the peptide CF3-Leu-Ala-NH-C6H4-CF3 (TFLA) with porcine pancreatic elastase. X-ray studies at 1.8 A.
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I.Li de la Sierra,
E.Papamichael,
C.Sakarellos,
J.L.Dimicoli,
T.Prangé.
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ABSTRACT
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The peptide trifluoroacetyl-Leu-Ala-(p-trifluoromethylanilide), is a reversible
inhibitor of pancreatic porcine elastase and is characterized by a Km of 2.5 x
10(-8) M. Co-crystals of the 1:1 complex were obtained in an acetate buffer +
dimethylformamide solution at pH 5.7. Diffraction data were recorded on films at
the LURE synchrotron facility. The inhibitor was localized on difference Fourier
maps, and the refinement of the structure was performed by simulated annealing
(XPLOR). The current agreement factor is R = 19% (for 13224 observed structure
factors and 1.8 A effective resolution). The RMS deviations from ideality of
bond distances and angles are 0.02 A and 2 degrees, respectively. The inhibitor
molecule was found in the active site, bent around the side chain of Phe-215 in
a geometry that resembles the previously reported structure of the CF3-Lys-Ala
complex at 2.5 A, in a parallel beta-sheet association with the loop 214-216.
The analysis of the close contacts (less than 3.5 A) indicates that the
trifluoromethylamide bond interacts with the active site and not the Leu-Ala or
Ala-anilide bonds. The two fluorinated groups of the inhibitor exhibit different
specificities: the trifluoroacetyl group (N terminus) is tightly stacked between
the two chain loops 191-195 and 213-215, while the trifluoromethylanilide (C
terminus) shows less specificity and only a single contact.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.Vulpetti,
N.Schiering,
and
C.Dalvit
(2010).
Combined use of computational chemistry, NMR screening, and X-ray crystallography for identification and characterization of fluorophilic protein environments.
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Proteins,
78,
3281-3291.
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PDB codes:
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I.Nakanishi,
T.Kinoshita,
A.Sato,
and
T.Tada
(2000).
Structure of porcine pancreatic elastase complexed with FR901277, a novel macrocyclic inhibitor of elastases, at 1.6 A resolution.
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Biopolymers,
53,
434-445.
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PDB code:
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M.M.Krem,
and
E.Di Cera
(1998).
Conserved water molecules in the specificity pocket of serine proteases and the molecular mechanism of Na+ binding.
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Proteins,
30,
34-42.
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M.C.Nicklaus,
S.Wang,
J.S.Driscoll,
and
G.W.Milne
(1995).
Conformational changes of small molecules binding to proteins.
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Bioorg Med Chem,
3,
411-428.
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W.F.Lau,
L.Tabernero,
J.S.Sack,
and
E.J.Iwanowicz
(1995).
Molecular modeling studies of novel retro-binding tripeptide active-site inhibitors of thrombin.
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Bioorg Med Chem,
3,
1039-1048.
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P.D.Edwards,
and
P.R.Bernstein
(1994).
Synthetic inhibitors of elastase.
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Med Res Rev,
14,
127-194.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
