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* Residue conservation analysis
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Enzyme class:
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Chain E:
E.C.3.4.21.4
- trypsin.
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Reaction:
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Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.
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J Mol Biol
230:919-933
(1993)
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PubMed id:
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Crystal structures of rat anionic trypsin complexed with the protein inhibitors APPI and BPTI.
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J.J.Perona,
C.A.Tsu,
C.S.Craik,
R.J.Fletterick.
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ABSTRACT
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The crystal structure of rat anionic trypsin D189G/G226D has been determined in
complexes with each of the protein inhibitors APPI (amyloid beta-protein
precursor inhibitor domain) and BPTI (bovine pancreatic trypsin inhibitor) at
resolutions of 2.5 A and 2.1 A, respectively. Comparisons with the structure of
the bovine trypsin-BPTI complex show that the enzyme-inhibitor interactions in
rat trypsin are dominated to a much greater degree by attractive and repulsive
electrostatic forces. Decreased structural complementarity in the flanking
regions of the interface formed with BPTI is reflected in significantly weaker
inhibition relative to bovine trypsin. The primary active site loop of BPTI
adopts slightly different conformations when bound to rat and cow trypsins,
reflecting a broader entrance to the binding pocket in the former. Tight
complementarity of each loop conformer to the respective active sites then gives
rise to significantly different overall orientations of the inhibitor when bound
to the two enzymes. The crystal structures of trypsin bound to these protein
inhibitors are excellent models of the Michaelis complexes, which permit
visualization of substrate interactions both N and C-terminal to the cleaved
bond, while maintaining identical reaction chemistry. They will be uniquely
useful to the structure-function analysis of variant rat trypsin enzymes.
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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.E.Swedberg,
S.J.de Veer,
and
J.M.Harris
(2010).
Natural and engineered kallikrein inhibitors: an emerging pharmacopoeia.
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Biol Chem,
391,
357-374.
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M.A.Salameh,
J.L.Robinson,
D.Navaneetham,
D.Sinha,
B.J.Madden,
P.N.Walsh,
and
E.S.Radisky
(2010).
The amyloid precursor protein/protease nexin 2 Kunitz inhibitor domain is a highly specific substrate of mesotrypsin.
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J Biol Chem,
285,
1939-1949.
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E.Zakharova,
M.P.Horvath,
and
D.P.Goldenberg
(2009).
Structure of a serine protease poised to resynthesize a peptide bond.
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Proc Natl Acad Sci U S A,
106,
11034-11039.
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PDB codes:
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Y.Feng,
M.Zhang,
M.Hu,
J.Zheng,
W.Jiao,
and
Z.Chang
(2009).
Disassembly intermediates of RbsD protein remain oligomeric despite the loss of an intact secondary structure.
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Sci China C Life Sci,
52,
997.
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S.K.Gara,
P.Grumati,
A.Urciuolo,
P.Bonaldo,
B.Kobbe,
M.Koch,
M.Paulsson,
and
R.Wagener
(2008).
Three novel collagen VI chains with high homology to the alpha3 chain.
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J Biol Chem,
283,
10658-10670.
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A.Kato,
K.Maki,
T.Ebina,
K.Kuwajima,
K.Soda,
and
Y.Kuroda
(2007).
Mutational analysis of protein solubility enhancement using short peptide tags.
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Biopolymers,
85,
12-18.
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A.Paju,
and
U.H.Stenman
(2006).
Biochemistry and clinical role of trypsinogens and pancreatic secretory trypsin inhibitor.
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Crit Rev Clin Lab Sci,
43,
103-142.
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T.T.Baird,
W.D.Wright,
and
C.S.Craik
(2006).
Conversion of trypsin to a functional threonine protease.
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Protein Sci,
15,
1229-1238.
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Y.Feng,
W.Jiao,
X.Fu,
and
Z.Chang
(2006).
Stepwise disassembly and apparent nonstepwise reassembly for the oligomeric RbsD protein.
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Protein Sci,
15,
1441-1448.
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A.Gudmundsdóttir
(2002).
Cold-adapted and mesophilic brachyurins.
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Biol Chem,
383,
1125-1131.
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A.Pasternak,
A.White,
C.J.Jeffery,
N.Medina,
M.Cahoon,
D.Ringe,
and
L.Hedstrom
(2001).
The energetic cost of induced fit catalysis: Crystal structures of trypsinogen mutants with enhanced activity and inhibitor affinity.
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Protein Sci,
10,
1331-1342.
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PDB codes:
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K.O.Badellino,
and
P.N.Walsh
(2000).
Protease nexin II interactions with coagulation factor XIa are contained within the Kunitz protease inhibitor domain of protease nexin II and the factor XIa catalytic domain.
|
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Biochemistry,
39,
4769-4777.
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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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A.Pasternak,
D.Ringe,
and
L.Hedstrom
(1999).
Comparison of anionic and cationic trypsinogens: the anionic activation domain is more flexible in solution and differs in its mode of BPTI binding in the crystal structure.
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Protein Sci,
8,
253-258.
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PDB codes:
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B.Gilquin,
A.Lecoq,
F.Desné,
M.Guenneugues,
S.Zinn-Justin,
and
A.Ménez
(1999).
Conformational and functional variability supported by the BPTI fold: solution structure of the Ca2+ channel blocker calcicludine.
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Proteins,
34,
520-532.
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PDB code:
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E.Szabó,
Z.Böcskei,
G.Náray-Szabó,
and
L.Gráf
(1999).
The three-dimensional structure of Asp189Ser trypsin provides evidence for an inherent structural plasticity of the protease.
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Eur J Biochem,
263,
20-26.
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PDB code:
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M.A.Qasim,
S.M.Lu,
J.Ding,
K.S.Bateman,
M.N.James,
S.Anderson,
J.Song,
J.L.Markley,
P.J.Ganz,
C.W.Saunders,
and
M.Laskowski
(1999).
Thermodynamic criterion for the conformation of P1 residues of substrates and of inhibitors in complexes with serine proteinases.
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Biochemistry,
38,
7142-7150.
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P.Ascenzi,
M.Ruoppolo,
A.Amoresano,
P.Pucci,
R.Consonni,
L.Zetta,
S.Pascarella,
F.Bortolotti,
and
E.Menegatti
(1999).
Characterization of low-molecular-mass trypsin isoinhibitors from oil-rape (Brassica napus var. oleifera) seed.
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Eur J Biochem,
261,
275-284.
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T.Kurth,
S.Grahn,
M.Thormann,
D.Ullmann,
H.J.Hofmann,
H.D.Jakubke,
and
L.Hedstrom
(1998).
Engineering the S1' subsite of trypsin: design of a protease which cleaves between dibasic residues.
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Biochemistry,
37,
11434-11440.
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A.J.Scheidig,
T.R.Hynes,
L.A.Pelletier,
J.A.Wells,
and
A.A.Kossiakoff
(1997).
Crystal structures of bovine chymotrypsin and trypsin complexed to the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) and basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with altered specificities.
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Protein Sci,
6,
1806-1824.
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PDB codes:
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C.Huang,
G.W.Wong,
N.Ghildyal,
M.F.Gurish,
A.Sali,
R.Matsumoto,
W.T.Qiu,
and
R.L.Stevens
(1997).
The tryptase, mouse mast cell protease 7, exhibits anticoagulant activity in vivo and in vitro due to its ability to degrade fibrinogen in the presence of the diverse array of protease inhibitors in plasma.
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J Biol Chem,
272,
31885-31893.
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C.N.Nyaruhucha,
M.Kito,
and
S.I.Fukuoka
(1997).
Identification and expression of the cDNA-encoding human mesotrypsin(ogen), an isoform of trypsin with inhibitor resistance.
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J Biol Chem,
272,
10573-10578.
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P.C.Hopkins,
W.S.Chang,
M.R.Wardell,
and
S.R.Stone
(1997).
Inhibitory mechanism of serpins. Mobility of the C-terminal region of the reactive-site loop.
|
| |
J Biol Chem,
272,
3905-3909.
|
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T.Kurth,
D.Ullmann,
H.D.Jakubke,
and
L.Hedstrom
(1997).
Converting trypsin to chymotrypsin: structural determinants of S1' specificity.
|
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Biochemistry,
36,
10098-10104.
|
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D.H.Shin,
H.K.Song,
I.S.Seong,
C.S.Lee,
C.H.Chung,
and
S.W.Suh
(1996).
Crystal structure analyses of uncomplexed ecotin in two crystal forms: implications for its function and stability.
|
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Protein Sci,
5,
2236-2247.
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PDB codes:
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L.Hedstrom,
T.Y.Lin,
and
W.Fast
(1996).
Hydrophobic interactions control zymogen activation in the trypsin family of serine proteases.
|
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Biochemistry,
35,
4515-4523.
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C.I.Wang,
Q.Yang,
and
C.S.Craik
(1995).
Isolation of a high affinity inhibitor of urokinase-type plasminogen activator by phage display of ecotin.
|
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J Biol Chem,
270,
12250-12256.
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J.J.Perona,
and
C.S.Craik
(1995).
Structural basis of substrate specificity in the serine proteases.
|
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Protein Sci,
4,
337-360.
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PDB code:
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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
