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PDBsum entry 1eld
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Hydrolase/hydrolase inhibitor
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PDB id
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1eld
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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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Structural analysis of the active site of porcine pancreatic elastase based on the X-Ray crystal structures of complexes with trifluoroacetyl-Dipeptide-Anilide inhibitors.
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Authors
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C.Mattos,
D.A.Giammona,
G.A.Petsko,
D.Ringe.
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Ref.
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Biochemistry, 1995,
34,
3193-3203.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
96%.
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Abstract
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The X-ray crystal structures of two new (trifluoroacetyl)dipeptide
p-(trifluoromethyl)anilide (TFA-dipeptide-TFM) inhibitors complexed to porcine
pancreatic elastase are presented. TFA-Val-Ala-TFM and TFA-Phe-Ala-TFM both bind
to elastase with the TFA group in the S1 subsite, Val or Phe in the S2 subsite,
Ala in the S3 subsite, and the TFM group in the S4 subsite. Five other
TFA-dipeptide-anilide/elastase crystal structures are available (two
TFA-X-Ala-p-(trifluoromethyl)anilide, X = Lys, Leu, and three
TFA-Lys-X-p-isopropylanilide, X = Pro, Leu, Phe). The four inhibitors with the
trifluoromethyl substituent on the anilide ring bind in a single mode to
elastase, whereas superposition of the three inhibitors with the isopropyl
substituent on the anilide ring show three different modes of binding to the
protein [Mattos, C., et al. (1994) Nature Struct. Biol. 1, 55-58]. The seven
structures are taken together in a detailed analysis of the active site of
porcine pancreatic elastase. The inhibition constants for the inhibitors are
used in combination with the crystal structures to understand the specificity of
the different elastase subsites.
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Secondary reference #1
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Title
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Analogous inhibitors of elastase do not always bind analogously.
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Authors
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C.Mattos,
B.Rasmussen,
X.Ding,
G.A.Petsko,
D.Ringe.
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Ref.
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Nat Struct Biol, 1994,
1,
55-58.
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PubMed id
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Secondary reference #2
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Title
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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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Authors
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I.Li de la sierra,
E.Papamichael,
C.Sakarellos,
J.L.Dimicoli,
T.Prangé.
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Ref.
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J Mol Recognit, 1990,
3,
36-44.
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PubMed id
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Secondary reference #3
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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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Secondary reference #4
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Title
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Structure of the product complex of acetyl-Ala-Pro-Ala with porcine pancreatic elastase at 1.65 a resolution.
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Authors
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E.F.Meyer,
R.Radhakrishnan,
G.M.Cole,
L.G.Presta.
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Ref.
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J Mol Biol, 1986,
189,
533-539.
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PubMed id
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Secondary reference #5
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Title
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Crystallographic study of the binding of a trifluoroacetyl dipeptide anilide inhibitor with elastase.
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Authors
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D.L.Hughes,
L.C.Sieker,
J.Bieth,
J.L.Dimicoli.
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Ref.
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J Mol Biol, 1982,
162,
645-658.
[DOI no: ]
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PubMed id
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Figure 1.
FIG. 1. Superposition f the inhibitor molecule and some neighbouring residues on the final difference
map (p,- IF,/) or TFAP in the active site region. Contours ar drawn at estimated lrvrls of 0,;5, I.0 and
1.5 I?.
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Figure 3.
FIG. 3. Th active centre region in: (a) native elastase (pH 5.0); (b) tosyl-elastase; and (c) the
TFAl/elastase complex, TFAP.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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Secondary reference #6
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Title
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The indirect mechanism of action of the trifluoroacetyl peptides on elastase. Enzymatic and 19f nmr studies.
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Authors
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J.L.Dimicoli,
A.Renaud,
J.Bieth.
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Ref.
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Eur J Biochem, 1980,
107,
423-432.
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PubMed id
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Secondary reference #7
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Title
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The atomic structure of crystalline porcine pancreatic elastase at 2.5 a resolution: comparisons with the structure of alpha-Chymotrypsin.
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Authors
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L.Sawyer,
D.M.Shotton,
J.W.Campbell,
P.L.Wendell,
H.Muirhead,
H.C.Watson.
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Ref.
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J Mol Biol, 1978,
118,
137-208.
[DOI no: ]
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PubMed id
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Figure 1.
FIG. 1. The variation in he ean arent and heavy-atom structure amplitudes and in he
accurctcy of the hase etermination of the complete high resolution tosyl-elastse data set as a
unction of sin20/ha. (-A-A-), F,//2 -O-O--), lfHl --m--W--, --O--O---,
--A--/--) and E (-m-m--, -e-a--, -b-A-) are defined as in Tables 3 and 4.
The values or wa are iven by the right ordinate, nd those or 1Frl, lfnl and E, which are n he
same non-absolute scale, by the ordinate. A, CMBS-elastase; 0, ranyl tosyl-elastase;
H, uranyl CMBS-elastase.
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Figure 10.
IG. 10. Histograms of (a) x, b) yz, (c) x3.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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