 |
PDBsum entry 3tgi
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Complex (serine protease/inhibitor)
|
PDB id
|
|
|
|
3tgi
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
Chain E:
E.C.3.4.21.4
- trypsin.
|
|
|
|
|
|
|
Reaction:
|
|
Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Protein Sci
8:253-258
(1999)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
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.
|
|
A.Pasternak,
D.Ringe,
L.Hedstrom.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Unlike bovine cationic trypsin, rat anionic trypsin retains activity at high pH.
This alkaline stability has been attributed to stabilization of the salt bridge
between the N-terminal Ile16 and Asp194 by the surface negative charge (Soman K,
Yang A-S, Honig B, Fletterick R., 1989, Biochemistry 28:9918-9926). The
formation of this salt bridge controls the conformation of the activation domain
in trypsin. In this work we probe the structure of rat trypsinogen to determine
the effects of the surface negative charge on the activation domain in the
absence of the Ile16-Asp194 salt bridge. We determined the crystal structures of
the rat trypsin-BPTI complex and the rat trypsinogen-BPTI complex at 1.8 and 2.2
A, respectively. The BPTI complex of rat trypsinogen resembles that of rat
trypsin. Surprisingly, the side chain of Ile16 is found in a similar position in
both the rat trypsin and trypsinogen complexes, although it is not the
N-terminal residue and cannot form the salt bridge in trypsinogen. The resulting
position of the activation peptide alters the conformation of the adjacent
autolysis loop (residues 142-153). While bovine trypsinogen and trypsin have
similar CD spectra, the CD spectrum of rat trypsinogen has only 60% of the
intensity of rat trypsin. This lower intensity most likely results from
increased flexibility around two conserved tryptophans, which are adjacent to
the activation domain. The NMR spectrum of rat trypsinogen contains high field
methyl signals as observed in bovine trypsinogen. It is concluded that the
activation domain of rat trypsinogen is more flexible than that of bovine
trypsinogen, but does not extend further into the protein core.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
E.Zakharova,
M.P.Horvath,
and
D.P.Goldenberg
(2009).
Structure of a serine protease poised to resynthesize a peptide bond.
|
| |
Proc Natl Acad Sci U S A,
106,
11034-11039.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
A.Muhlia-Almazán,
A.Sánchez-Paz,
and
F.L.García-Carreño
(2008).
Invertebrate trypsins: a review.
|
| |
J Comp Physiol [B],
178,
655-672.
|
|
|
|
|
|
|
A.E.Aleshin,
S.A.Shiryaev,
A.Y.Strongin,
and
R.C.Liddington
(2007).
Structural evidence for regulation and specificity of flaviviral proteases and evolution of the Flaviviridae fold.
|
| |
Protein Sci,
16,
795-806.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
S.Q.Liu,
Z.H.Meng,
J.K.Yang,
Y.X.Fu,
and
K.Q.Zhang
(2007).
Characterizing structural features of cuticle-degrading proteases from fungi by molecular modeling.
|
| |
BMC Struct Biol,
7,
33.
|
|
|
|
|
|
|
O.Király,
L.Guan,
E.Szepessy,
M.Tóth,
Z.Kukor,
and
M.Sahin-Tóth
(2006).
Expression of human cationic trypsinogen with an authentic N terminus using intein-mediated splicing in aminopeptidase P deficient Escherichia coli.
|
| |
Protein Expr Purif,
48,
104-111.
|
|
|
|
|
|
|
J.Arnórsdóttir,
M.M.Kristjánsson,
and
R.Ficner
(2005).
Crystal structure of a subtilisin-like serine proteinase from a psychrotrophic Vibrio species reveals structural aspects of cold adaptation.
|
| |
FEBS J,
272,
832-845.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
T.S.Zamolodchikova,
E.V.Smirnova,
A.N.Andrianov,
I.V.Kashparov,
O.D.Kotsareva,
E.A.Sokolova,
K.B.Ignatov,
and
A.D.Pemberton
(2005).
Cloning and molecular modeling of duodenase with respect to evolution of substrate specificity within mammalian serine proteases that have lost a conserved active-site disulfide bond.
|
| |
Biochemistry (Mosc),
70,
672-684.
|
|
|
|
|
|
|
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.
|
| |
Protein Sci,
10,
1331-1342.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
S.Ye,
A.L.Cech,
R.Belmares,
R.C.Bergstrom,
Y.Tong,
D.R.Corey,
M.R.Kanost,
and
E.J.Goldsmith
(2001).
The structure of a Michaelis serpin-protease complex.
|
| |
Nat Struct Biol,
8,
979-983.
|
|
|
PDB codes:
|
|
|
|
|
|
|
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.
|
|
|
Links
