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* Residue conservation analysis
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Enzyme class:
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Chain E:
E.C.3.4.21.1
- chymotrypsin.
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Reaction:
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Preferential cleavage: Tyr-|-Xaa, Trp-|-Xaa, Phe-|-Xaa, Leu-|-Xaa.
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J Mol Biol
220:711-722
(1991)
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PubMed id:
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Three-dimensional structure of the complexes between bovine chymotrypsinogen A and two recombinant variants of human pancreatic secretory trypsin inhibitor (Kazal-type).
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H.J.Hecht,
M.Szardenings,
J.Collins,
D.Schomburg.
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ABSTRACT
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Variants of the human pancreatic secretory trypsin inhibitor (PSTI) have been
created during a protein design project to generate a high-affinity inhibitor
with respect to some serine proteases other than trypsin. Two modified versions
of human PSTI with high affinity for chymotrypsin were crystallized as a complex
with chymotrypsinogen. Both crystallize isomorphously in space group P4(1)2(1)2
with lattice constants a = 84.4 A, c = 86.7 A and diffract to 2.3 A resolution.
The structure was solved by molecular replacement. The final R-value after
refinement with 8.0 to 2.3 A resolution data was 19.5% for both complexes after
inclusion of about 50 bound water molecules. The overall three-dimensional
structure of PSTI is similar to the structure of porcine PSTI in the trypsinogen
complex (1TGS). Small differences in the relative orientation of the binding
loop and the core of the inhibitors indicate flexible adaptation to the
proteases. The chymotrypsinogen part of the complex is similar to chymotrypsin.
After refolding induced by binding of the inhibitor the root-mean-square
difference of the active site residues A186 to A195 and A217 to A222 compared to
chymotrypsin was 0.26 A.
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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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J.Martin,
L.Regad,
C.Etchebest,
and
A.C.Camproux
(2008).
Taking advantage of local structure descriptors to analyze interresidue contacts in protein structures and protein complexes.
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Proteins,
73,
672-689.
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K.Bastard,
C.Prévost,
and
M.Zacharias
(2006).
Accounting for loop flexibility during protein-protein docking.
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Proteins,
62,
956-969.
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L.Jiang,
Y.Gao,
F.Mao,
Z.Liu,
and
L.Lai
(2002).
Potential of mean force for protein-protein interaction studies.
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Proteins,
46,
190-196.
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S.M.Lu,
W.Lu,
M.A.Qasim,
S.Anderson,
I.Apostol,
W.Ardelt,
T.Bigler,
Y.W.Chiang,
J.Cook,
M.N.James,
I.Kato,
C.Kelly,
W.Kohr,
T.Komiyama,
T.Y.Lin,
M.Ogawa,
J.Otlewski,
S.J.Park,
S.Qasim,
M.Ranjbar,
M.Tashiro,
N.Warne,
H.Whatley,
A.Wieczorek,
M.Wieczorek,
T.Wilusz,
R.Wynn,
W.Zhang,
and
M.Laskowski
(2001).
Predicting the reactivity of proteins from their sequence alone: Kazal family of protein inhibitors of serine proteinases.
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Proc Natl Acad Sci U S A,
98,
1410-1415.
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A.Mac Sweeney,
G.Birrane,
M.A.Walsh,
T.O'Connell,
J.P.Malthouse,
and
T.M.Higgins
(2000).
Crystal structure of delta-chymotrypsin bound to a peptidyl chloromethyl ketone inhibitor.
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Acta Crystallogr D Biol Crystallogr,
56,
280-286.
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PDB code:
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D.W.Ritchie,
and
G.J.Kemp
(2000).
Protein docking using spherical polar Fourier correlations.
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Proteins,
39,
178-194.
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G.Barbato,
D.O.Cicero,
F.Cordier,
F.Narjes,
B.Gerlach,
S.Sambucini,
S.Grzesiek,
V.G.Matassa,
R.De Francesco,
and
R.Bazzo
(2000).
Inhibitor binding induces active site stabilization of the HCV NS3 protein serine protease domain.
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EMBO J,
19,
1195-1206.
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PDB code:
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V.Z.Pletnev,
T.S.Zamolodchikova,
W.A.Pangborn,
and
W.L.Duax
(2000).
Crystal structure of bovine duodenase, a serine protease, with dual trypsin and chymotrypsin-like specificities.
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Proteins,
41,
8.
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PDB code:
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G.Moont,
H.A.Gabb,
and
M.J.Sternberg
(1999).
Use of pair potentials across protein interfaces in screening predicted docked complexes.
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Proteins,
35,
364-373.
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H.Jing,
K.J.Macon,
D.Moore,
L.J.DeLucas,
J.E.Volanakis,
and
S.V.Narayana
(1999).
Structural basis of profactor D activation: from a highly flexible zymogen to a novel self-inhibited serine protease, complement factor D.
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EMBO J,
18,
804-814.
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PDB code:
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C.Capasso,
M.Rizzi,
E.Menegatti,
P.Ascenzi,
and
M.Bolognesi
(1997).
Crystal structure of the bovine alpha-chymotrypsin:Kunitz inhibitor complex. An example of multiple protein:protein recognition sites.
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J Mol Recognit,
10,
26-35.
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PDB code:
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P.Ascenzi,
G.Amiconi,
W.Bode,
M.Bolognesi,
M.Coletta,
and
E.Menegatti
(1995).
Proteinase inhibitors from the European medicinal leech Hirudo medicinalis: structural, functional and biomedical aspects.
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Mol Aspects Med,
16,
215-313.
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C.L.Fisher,
J.S.Greengard,
and
J.H.Griffin
(1994).
Models of the serine protease domain of the human antithrombotic plasma factor activated protein C and its zymogen.
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Protein Sci,
3,
588-599.
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PDB codes:
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W.Bode,
and
R.Huber
(1992).
Natural protein proteinase inhibitors and their interaction with proteinases.
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Eur J Biochem,
204,
433-451.
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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
code is
shown on the right.
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Links
