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PDBsum entry 1ton
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Hydrolase(serine proteinase)
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PDB id
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1ton
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.21.35
- tissue kallikrein.
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Reaction:
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Preferential cleavage of Arg-|-Xaa bonds in small molecule substrates. Highly selective action to release kallidin (lysyl-bradykinin) from kininogen involves hydrolysis of Met-|-Xaa or Leu-|-Xaa. The rat enzyme is unusual in liberating bradykinin directly from autologous kininogens by cleavage at two Arg-|-Xaa bonds.
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J Mol Biol
195:373-396
(1987)
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PubMed id:
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Rat submaxillary gland serine protease, tonin. Structure solution and refinement at 1.8 A resolution.
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M.Fujinaga,
M.N.James.
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ABSTRACT
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Tonin is a mammalian serine protease that is capable of generating the
vasoconstrictive agent, angiotensin II, directly from its precursor protein,
angiotensinogen, a process that normally requires two enzymes, renin and
angiotensin-converting enzyme. The X-ray crystallographic structure
determination and refinement of tonin at 1.8 A resolution and the analysis of
the resulting model are reported. The initial phases were obtained by the method
of molecular replacement using as the search model the structure of bovine
trypsin. The refined model of tonin consists of 227 amino acid residues out of
the 235 in the complete molecule, 149 water molecules, and one zinc ion. The
R-factor (R = sigma Fo - Fc/sigma Fo) is 0.196 for the 14,997 measured data
between 8 and 1.8 A resolution with I greater than or equal to sigma (I). It is
estimated that the overall root-mean-square error in the coordinates is about
0.3 A. The structure of tonin that has been determined is not in its active
conformation, but one that has been perturbed by the binding of Zn2+ in the
active site. Zn2+ was included in the buffer to aid the crystallization.
Nevertheless, the structure of tonin that is described is for the most part
similar to its native form as indicated by the close tertiary structural
homology with kallikrein. The differences in the structures of the two enzymes
are concentrated in several loop regions; these structural differences are
probably responsible for the differences in their reactivities and specificities.
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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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E.Krissinel
(2011).
Macromolecular complexes in crystals and solutions.
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Acta Crystallogr D Biol Crystallogr,
67,
376-385.
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C.Eigenbrot,
R.Ganesan,
and
D.Kirchhofer
(2010).
Hepatocyte growth factor activator (HGFA): molecular structure and interactions with HGFA inhibitor-1 (HAI-1).
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FEBS J,
277,
2215-2222.
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P.Goettig,
V.Magdolen,
and
H.Brandstetter
(2010).
Natural and synthetic inhibitors of kallikrein-related peptidases (KLKs).
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Biochimie,
92,
1546-1567.
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J.A.Clements
(2008).
Reflections on the tissue kallikrein and kallikrein-related peptidase family - from mice to men - what have we learnt in the last two decades?
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Biol Chem,
389,
1447-1454.
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G.Prehna,
and
C.E.Stebbins
(2007).
A Rac1-GDP trimer complex binds zinc with tetrahedral and octahedral coordination, displacing magnesium.
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Acta Crystallogr D Biol Crystallogr,
63,
628-635.
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PDB code:
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M.Debela,
P.Hess,
V.Magdolen,
N.M.Schechter,
T.Steiner,
R.Huber,
W.Bode,
and
P.Goettig
(2007).
Chymotryptic specificity determinants in the 1.0 A structure of the zinc-inhibited human tissue kallikrein 7.
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Proc Natl Acad Sci U S A,
104,
16086-16091.
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PDB codes:
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K.Segers,
J.Rosing,
and
G.A.Nicolaes
(2006).
Structural models of the snake venom factor V activators from Daboia russelli and Daboia lebetina.
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Proteins,
64,
968-984.
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PDB codes:
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M.Debela,
V.Magdolen,
N.Schechter,
M.Valachova,
F.Lottspeich,
C.S.Craik,
Y.Choe,
W.Bode,
and
P.Goettig
(2006).
Specificity profiling of seven human tissue kallikreins reveals individual subsite preferences.
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J Biol Chem,
281,
25678-25688.
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G.Laxmikanthan,
S.I.Blaber,
M.J.Bernett,
I.A.Scarisbrick,
M.A.Juliano,
and
M.Blaber
(2005).
1.70 A X-ray structure of human apo kallikrein 1: structural changes upon peptide inhibitor/substrate binding.
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Proteins,
58,
802-814.
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PDB code:
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T.Hamelryck
(2003).
Efficient identification of side-chain patterns using a multidimensional index tree.
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Proteins,
51,
96.
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F.X.Gomis-Rüth,
A.Bayés,
G.Sotiropoulou,
G.Pampalakis,
T.Tsetsenis,
V.Villegas,
F.X.Avilés,
and
M.Coll
(2002).
The structure of human prokallikrein 6 reveals a novel activation mechanism for the kallikrein family.
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J Biol Chem,
277,
27273-27281.
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PDB code:
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M.C.Hsieh,
and
B.S.Cooperman
(2002).
Inhibition of prostate-specific antigen (PSA) by alpha(1)-antichymotrypsin: salt-dependent activation mediated by a conformational change.
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Biochemistry,
41,
2990-2997.
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H.Ponstingl,
K.Henrick,
and
J.M.Thornton
(2000).
Discriminating between homodimeric and monomeric proteins in the crystalline state.
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Proteins,
41,
47-57.
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J.D.Szustakowski,
and
Z.Weng
(2000).
Protein structure alignment using a genetic algorithm.
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Proteins,
38,
428-440.
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H.Czapinska,
and
J.Otlewski
(1999).
Structural and energetic determinants of the S1-site specificity in serine proteases.
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Eur J Biochem,
260,
571-595.
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K.Sekar,
and
M.Sundaralingam
(1999).
High-resolution refinement of orthorhombic bovine pancreatic phospholipase A2.
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Acta Crystallogr D Biol Crystallogr,
55,
46-50.
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PDB code:
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K.Sekar,
R.Biswas,
Y.Li,
M.Tsai,
and
M.Sundaralingam
(1999).
Structures of the catalytic site mutants D99A and H48Q and the calcium-loop mutant D49E of phospholipase A2.
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Acta Crystallogr D Biol Crystallogr,
55,
443-447.
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PDB codes:
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M.A.Juliano,
F.Filira,
M.Gobbo,
R.Rocchi,
E.Del Nery,
and
L.Juliano
(1999).
Chromogenic and fluorogenic glycosylated and acetylglycosylated peptides as substrates for serine, thiol and aspartyl proteases.
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J Pept Res,
53,
109-119.
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G.S.Coombs,
R.C.Bergstrom,
J.L.Pellequer,
S.I.Baker,
M.Navre,
M.M.Smith,
J.A.Tainer,
E.L.Madison,
and
D.R.Corey
(1998).
Substrate specificity of prostate-specific antigen (PSA).
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Chem Biol,
5,
475-488.
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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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A.C.Wallace,
N.Borkakoti,
and
J.M.Thornton
(1997).
TESS: a geometric hashing algorithm for deriving 3D coordinate templates for searching structural databases. Application to enzyme active sites.
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Protein Sci,
6,
2308-2323.
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B.Bax,
T.L.Blundell,
J.Murray-Rust,
and
N.Q.McDonald
(1997).
Structure of mouse 7S NGF: a complex of nerve growth factor with four binding proteins.
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Structure,
5,
1275-1285.
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PDB code:
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D.E.Timm
(1997).
The crystal structure of the mouse glandular kallikrein-13 (prorenin converting enzyme).
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Protein Sci,
6,
1418-1425.
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PDB code:
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B.O.Villoutreix,
H.Lilja,
K.Pettersson,
T.Lövgren,
and
O.Teleman
(1996).
Structural investigation of the alpha-1-antichymotrypsin: prostate-specific antigen complex by comparative model building.
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Protein Sci,
5,
836-851.
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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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N.C.Singha,
N.Surolia,
and
A.Surolia
(1996).
On the relationship of thermodynamic parameters with the buried surface area in protein-ligand complex formation.
|
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Biosci Rep,
16,
1.
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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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A.A.Adzhubei,
and
M.J.Sternberg
(1994).
Conservation of polyproline II helices in homologous proteins: implications for structure prediction by model building.
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Protein Sci,
3,
2395-2410.
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B.O.Villoutreix,
E.D.Getzoff,
and
J.H.Griffin
(1994).
A structural model for the prostate disease marker, human prostate-specific antigen.
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Protein Sci,
3,
2033-2044.
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PDB code:
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E.Pizzi,
A.Tramontano,
L.Tomei,
N.La Monica,
C.Failla,
M.Sardana,
T.Wood,
and
R.De Francesco
(1994).
Molecular model of the specificity pocket of the hepatitis C virus protease: implications for substrate recognition.
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Proc Natl Acad Sci U S A,
91,
888-892.
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T.N.Bhat,
G.A.Bentley,
G.Boulot,
M.I.Greene,
D.Tello,
W.Dall'Acqua,
H.Souchon,
F.P.Schwarz,
R.A.Mariuzza,
and
R.J.Poljak
(1994).
Bound water molecules and conformational stabilization help mediate an antigen-antibody association.
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Proc Natl Acad Sci U S A,
91,
1089-1093.
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PDB codes:
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A.W.Chan,
E.G.Hutchinson,
D.Harris,
and
J.M.Thornton
(1993).
Identification, classification, and analysis of beta-bulges in proteins.
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Protein Sci,
2,
1574-1590.
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B.Bax,
M.Blaber,
G.Ferguson,
M.J.Sternberg,
and
P.H.Walls
(1993).
Prediction of the three-dimensional structures of the nerve growth factor and epidermal growth factor binding proteins (kallikreins) and an hypothetical structure of the high molecular weight complex of epidermal growth factor with its binding protein.
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Protein Sci,
2,
1229-1241.
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C.S.Ring,
E.Sun,
J.H.McKerrow,
G.K.Lee,
P.J.Rosenthal,
I.D.Kuntz,
and
F.E.Cohen
(1993).
Structure-based inhibitor design by using protein models for the development of antiparasitic agents.
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Proc Natl Acad Sci U S A,
90,
3583-3587.
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E.Meyer
(1992).
Internal water molecules and H-bonding in biological macromolecules: a review of structural features with functional implications.
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Protein Sci,
1,
1543-1562.
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J.N.Higaki,
R.J.Fletterick,
and
C.S.Craik
(1992).
Engineered metalloregulation in enzymes.
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Trends Biochem Sci,
17,
100-104.
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P.M.Hecht,
and
K.V.Anderson
(1992).
Extracellular proteases and embryonic pattern formation.
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Trends Cell Biol,
2,
197-202.
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B.F.Le Bonniec,
and
C.T.Esmon
(1991).
Glu-192----Gln substitution in thrombin mimics the catalytic switch induced by thrombomodulin.
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Proc Natl Acad Sci U S A,
88,
7371-7375.
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J.Rose,
and
F.Eisenmenger
(1991).
A fast unbiased comparison of protein structures by means of the Needleman-Wunsch algorithm.
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J Mol Evol,
32,
340-354.
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O.Herzberg,
and
J.Moult
(1991).
Analysis of the steric strain in the polypeptide backbone of protein molecules.
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Proteins,
11,
223-229.
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J.Greer
(1990).
Comparative modeling methods: application to the family of the mammalian serine proteases.
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Proteins,
7,
317-334.
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M.S.Johnson,
M.J.Sutcliffe,
and
T.L.Blundell
(1990).
Molecular anatomy: phyletic relationships derived from three-dimensional structures of proteins.
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J Mol Evol,
30,
43-59.
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M.E.Murphy,
J.Moult,
R.C.Bleackley,
H.Gershenfeld,
I.L.Weissman,
and
M.N.James
(1988).
Comparative molecular model building of two serine proteinases from cytotoxic T lymphocytes.
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Proteins,
4,
190-204.
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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
