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PDBsum entry 1att
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Serine proteinase inhibitor
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PDB id
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1att
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Contents |
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* Residue conservation analysis
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J Mol Biol
232:223-241
(1993)
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PubMed id:
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Crystal structure of cleaved bovine antithrombin III at 3.2 A resolution.
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L.Mourey,
J.P.Samama,
M.Delarue,
M.Petitou,
J.Choay,
D.Moras.
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ABSTRACT
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The crystal structure of cleaved antithrombin III (ATIII) has been determined to
3.2 A resolution by single isomorphous replacement, real space density
modification and phase extension protocols. The heavy-atom sites and the first
molecular envelope were determined owing to the molecular replacement solution
previously reported and partially refined. Refinement of the two molecules of
the asymmetric unit led to a crystallographic R-factor of 0.212 for all
reflections between 8.0 and 3.2 A, without inclusion of water molecules. The
root-mean-square deviation from ideal values is, respectively, 0.015 A and 3.6
degrees for bond lengths and bond angles. The topology of the molecule closely
resembles that of cleaved serpins inhibitors with the two residues forming the
reactive bond at opposite ends of the molecule. The most significant difference
between ATIII and alpha 1-antitrypsin lies in the 45 residue N-terminal
extension in ATIII which contribute to the definition of the heparin binding
site. This loop region at the surface of the molecule is held by two disulphide
bridges to the protein core and exhibits high temperature factor values. It
forms a valley which restrains the possibilities for binding of heparin. Docking
of the pentasaccharide unit which represents the minimum fragment of heparin
able to bind to ATIII indicates a possible role for arginine 14 in the
interaction of heparin and the protein.
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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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D.Krilleke,
A.DeErkenez,
W.Schubert,
I.Giri,
G.S.Robinson,
Y.S.Ng,
and
D.T.Shima
(2007).
Molecular mapping and functional characterization of the VEGF164 heparin-binding domain.
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J Biol Chem,
282,
28045-28056.
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W.Zhang,
R.Swanson,
Y.Xiong,
B.Richard,
and
S.T.Olson
(2006).
Antiangiogenic antithrombin blocks the heparan sulfate-dependent binding of proangiogenic growth factors to their endothelial cell receptors: evidence for differential binding of antiangiogenic and anticoagulant forms of antithrombin to proangiogenic heparan sulfate domains.
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J Biol Chem,
281,
37302-37310.
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W.Zhang,
R.Swanson,
G.Izaguirre,
Y.Xiong,
L.F.Lau,
and
S.T.Olson
(2005).
The heparin-binding site of antithrombin is crucial for antiangiogenic activity.
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Blood,
106,
1621-1628.
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G.L.Long,
M.Kjellberg,
B.O.Villoutreix,
and
J.Stenflo
(2003).
Probing plasma clearance of the thrombin-antithrombin complex with a monoclonal antibody against the putative serpin-enzyme complex receptor-binding site.
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Eur J Biochem,
270,
4059-4069.
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K.J.Belzar,
A.Zhou,
R.W.Carrell,
P.G.Gettins,
and
J.A.Huntington
(2002).
Helix D elongation and allosteric activation of antithrombin.
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J Biol Chem,
277,
8551-8558.
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R.Geiben-Lynn,
N.Brown,
B.D.Walker,
and
A.D.Luster
(2002).
Purification of a modified form of bovine antithrombin III as an HIV-1 CD8+ T-cell antiviral factor.
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J Biol Chem,
277,
42352-42357.
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M.Renatus,
Q.Zhou,
H.R.Stennicke,
S.J.Snipas,
D.Turk,
L.A.Bankston,
R.C.Liddington,
and
G.S.Salvesen
(2000).
Crystal structure of the apoptotic suppressor CrmA in its cleaved form.
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Structure,
8,
789-797.
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PDB code:
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M.Simonovic,
Gettins PGW,
and
K.Volz
(2000).
Crystal structure of viral serpin crmA provides insights into its mechanism of cysteine proteinase inhibition.
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Protein Sci,
9,
1423-1427.
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PDB codes:
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P.R.Elliott,
X.Y.Pei,
T.R.Dafforn,
and
D.A.Lomas
(2000).
Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets for rational drug design to prevent conformational disease.
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Protein Sci,
9,
1274-1281.
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PDB code:
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A.Lombardi,
G.De Simone,
S.Galdiero,
N.Staiano,
F.Nastri,
and
V.Pavone
(1999).
From natural to synthetic multisite thrombin inhibitors.
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Biopolymers,
51,
19-39.
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A.Sharma,
J.A.Askari,
M.J.Humphries,
E.Y.Jones,
and
D.I.Stuart
(1999).
Crystal structure of a heparin- and integrin-binding segment of human fibronectin.
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EMBO J,
18,
1468-1479.
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PDB code:
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M.S.O'Reilly,
S.Pirie-Shepherd,
W.S.Lane,
and
J.Folkman
(1999).
Antiangiogenic activity of the cleaved conformation of the serpin antithrombin.
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Science,
285,
1926-1928.
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V.Picard,
P.E.Marque,
F.Paolucci,
M.Aiach,
and
B.F.Le Bonniec
(1999).
Topology of the stable serpin-protease complexes revealed by an autoantibody that fails to react with the monomeric conformers of antithrombin.
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J Biol Chem,
274,
4586-4593.
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C.M.Lukacs,
H.Rubin,
and
D.W.Christianson
(1998).
Engineering an anion-binding cavity in antichymotrypsin modulates the "spring-loaded" serpin-protease interaction.
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Biochemistry,
37,
3297-3304.
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PDB codes:
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E.Trybala,
T.Bergström,
D.Spillmann,
B.Svennerholm,
S.J.Flynn,
and
P.Ryan
(1998).
Interaction between pseudorabies virus and heparin/heparan sulfate. Pseudorabies virus mutants differ in their interaction with heparin/heparan sulfate when altered for specific glycoprotein C heparin-binding domain.
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J Biol Chem,
273,
5047-5052.
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J.L.Meagher,
J.M.Beechem,
S.T.Olson,
and
P.G.Gettins
(1998).
Deconvolution of the fluorescence emission spectrum of human antithrombin and identification of the tryptophan residues that are responsive to heparin binding.
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J Biol Chem,
273,
23283-23289.
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J.Whisstock,
R.Skinner,
and
A.M.Lesk
(1998).
An atlas of serpin conformations.
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Trends Biochem Sci,
23,
63-67.
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L.Chakravarty,
L.Rogers,
T.Quach,
S.Breckenridge,
and
P.E.Kolattukudy
(1998).
Lysine 58 and histidine 66 at the C-terminal alpha-helix of monocyte chemoattractant protein-1 are essential for glycosaminoglycan binding.
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J Biol Chem,
273,
29641-29647.
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C.J.van Delden,
J.P.Lens,
R.P.Kooyman,
G.H.Engbers,
and
J.Feijen
(1997).
Heparinization of gas plasma-modified polystyrene surfaces and the interactions of these surfaces with proteins studied with surface plasmon resonance.
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Biomaterials,
18,
845-852.
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E.Ersdal-Badju,
A.Lu,
Y.Zuo,
V.Picard,
and
S.C.Bock
(1997).
Identification of the antithrombin III heparin binding site.
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J Biol Chem,
272,
19393-19400.
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G.Kaslik,
J.Kardos,
E.Szabó,
L.Szilágyi,
P.Závodszky,
W.M.Westler,
J.L.Markley,
and
L.Gráf
(1997).
Effects of serpin binding on the target proteinase: global stabilization, localized increased structural flexibility, and conserved hydrogen bonding at the active site.
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Biochemistry,
36,
5455-5464.
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L.Jin,
J.P.Abrahams,
R.Skinner,
M.Petitou,
R.N.Pike,
and
R.W.Carrell
(1997).
The anticoagulant activation of antithrombin by heparin.
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Proc Natl Acad Sci U S A,
94,
14683-14688.
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PDB code:
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S.Di Marco,
and
J.P.Priestle
(1997).
Structure of the complex of leech-derived tryptase inhibitor (LDTI) with trypsin and modeling of the LDTI-tryptase system.
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Structure,
5,
1465-1474.
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PDB code:
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W.S.Chang,
J.Whisstock,
P.C.Hopkins,
A.M.Lesk,
R.W.Carrell,
and
M.R.Wardell
(1997).
Importance of the release of strand 1C to the polymerization mechanism of inhibitory serpins.
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Protein Sci,
6,
89-98.
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A.J.Schulze,
D.Quarzago,
and
P.A.Andreasen
(1996).
A spectroscopic study of the structures of latent, active and reactive-center-cleaved type-1 plasminogen-activator inhibitor.
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Eur J Biochem,
240,
550-555.
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C.M.Lukacs,
J.Q.Zhong,
M.I.Plotnick,
H.Rubin,
B.S.Cooperman,
and
D.W.Christianson
(1996).
Arginine substitutions in the hinge region of antichymotrypsin affect serpin beta-sheet rearrangement.
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Nat Struct Biol,
3,
888-893.
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PDB codes:
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D.A.Lane,
G.Kunz,
R.J.Olds,
and
S.L.Thein
(1996).
Molecular genetics of antithrombin deficiency.
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Blood Rev,
10,
59-74.
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D.J.Perry,
and
R.W.Carrell
(1996).
Molecular genetics of human antithrombin deficiency.
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Hum Mutat,
7,
7.
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H.Koloczek,
A.Banbula,
G.S.Salvesen,
and
J.Potempa
(1996).
Serpin alpha 1proteinase inhibitor probed by intrinsic tryptophan fluorescence spectroscopy.
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Protein Sci,
5,
2226-2235.
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H.T.Wright
(1996).
The structural puzzle of how serpin serine proteinase inhibitors work.
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Bioessays,
18,
453-464.
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J.A.Huntington,
S.T.Olson,
B.Fan,
and
P.G.Gettins
(1996).
Mechanism of heparin activation of antithrombin. Evidence for reactive center loop preinsertion with expulsion upon heparin binding.
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Biochemistry,
35,
8495-8503.
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J.Whisstock,
A.M.Lesk,
and
R.Carrell
(1996).
Modeling of serpin-protease complexes: antithrombin-thrombin, alpha 1-antitrypsin (358Met-->Arg)-thrombin, alpha 1-antitrypsin (358Met-->Arg)-trypsin, and antitrypsin-elastase.
|
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Proteins,
26,
288-303.
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K.Nordling,
and
I.Björk
(1996).
Identification of an epitope in antithrombin appearing on insertion of the reactive-bond loop into the A beta-sheet.
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Biochemistry,
35,
10436-10440.
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R.W.Carrell,
and
P.E.Stein
(1996).
The biostructural pathology of the serpins: critical function of sheet opening mechanism.
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Biol Chem Hoppe Seyler,
377,
1.
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S.E.Ryu,
H.J.Choi,
K.S.Kwon,
K.N.Lee,
and
M.H.Yu
(1996).
The native strains in the hydrophobic core and flexible reactive loop of a serine protease inhibitor: crystal structure of an uncleaved alpha1-antitrypsin at 2.7 A.
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Structure,
4,
1181-1192.
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PDB code:
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C.Oxvig,
J.Haaning,
L.Kristensen,
J.M.Wagner,
I.Rubin,
T.Stigbrand,
G.J.Gleich,
and
L.Sottrup-Jensen
(1995).
Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma.
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J Biol Chem,
270,
13645-13651.
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D.A.Lomas,
P.R.Elliott,
S.K.Sidhar,
R.C.Foreman,
J.T.Finch,
D.W.Cox,
J.C.Whisstock,
and
R.W.Carrell
(1995).
alpha 1-Antitrypsin Mmalton (Phe52-deleted) forms loop-sheet polymers in vivo. Evidence for the C sheet mechanism of polymerization.
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J Biol Chem,
270,
16864-16870.
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D.A.Lomas,
P.R.Elliott,
W.S.Chang,
M.R.Wardell,
and
R.W.Carrell
(1995).
Preparation and characterization of latent alpha 1-antitrypsin.
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J Biol Chem,
270,
5282-5288.
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H.T.Wright,
and
J.N.Scarsdale
(1995).
Structural basis for serpin inhibitor activity.
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Proteins,
22,
210-225.
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S.Ernst,
R.Langer,
C.L.Cooney,
and
R.Sasisekharan
(1995).
Enzymatic degradation of glycosaminoglycans.
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Crit Rev Biochem Mol Biol,
30,
387-444.
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T.F.Busby,
W.S.Argraves,
S.A.Brew,
I.Pechik,
G.L.Gilliland,
and
K.C.Ingham
(1995).
Heparin binding by fibronectin module III-13 involves six discontinuous basic residues brought together to form a cationic cradle.
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J Biol Chem,
270,
18558-18562.
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A.Wei,
H.Rubin,
B.S.Cooperman,
and
D.W.Christianson
(1994).
Crystal structure of an uncleaved serpin reveals the conformation of an inhibitory reactive loop.
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Nat Struct Biol,
1,
251-258.
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C.A.van Boeckel,
P.D.Grootenhuis,
and
A.Visser
(1994).
A mechanism for heparin-induced potentiation of antithrombin III.
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Nat Struct Biol,
1,
423-425.
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D.Bruce,
D.J.Perry,
J.Y.Borg,
R.W.Carrell,
and
M.R.Wardell
(1994).
Thromboembolic disease due to thermolabile conformational changes of antithrombin Rouen-VI (187 Asn-->Asp)
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J Clin Invest,
94,
2265-2274.
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D.J.Perry
(1994).
Antithrombin and its inherited deficiencies.
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Blood Rev,
8,
37-55.
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H.A.Schreuder,
B.de Boer,
R.Dijkema,
J.Mulders,
H.J.Theunissen,
P.D.Grootenhuis,
and
W.G.Hol
(1994).
The intact and cleaved human antithrombin III complex as a model for serpin-proteinase interactions.
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Nat Struct Biol,
1,
48-54.
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PDB code:
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M.T.Stubbs,
and
W.Bode
(1994).
Coagulation factors and their inhibitors.
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Curr Opin Struct Biol,
4,
823-832.
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R.W.Carrell,
P.E.Stein,
G.Fermi,
and
M.R.Wardell
(1994).
Biological implications of a 3 A structure of dimeric antithrombin.
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Structure,
2,
257-270.
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PDB code:
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S.S.Twining
(1994).
Regulation of proteolytic activity in tissues.
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Crit Rev Biochem Mol Biol,
29,
315-383.
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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
