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* Residue conservation analysis
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Enzyme class:
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Chain A:
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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DOI no:
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J Mol Biol
275:347-363
(1998)
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PubMed id:
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Kunitz-type soybean trypsin inhibitor revisited: refined structure of its complex with porcine trypsin reveals an insight into the interaction between a homologous inhibitor from Erythrina caffra and tissue-type plasminogen activator.
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H.K.Song,
S.W.Suh.
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ABSTRACT
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The Kunitz-type trypsin inhibitor from soybean (STI) consists of 181 amino acid
residues with two disulfide bridges. Its crystal structures have been determined
in complex with porcine pancreatic trypsin in two crystal forms (an orthorhombic
form at 1.75 A resolution and a tetragonal form at 1.9 A) and in the free state
at 2.3 A resolution. They have been refined to crystallographic R-values of
18.9%, 21.6% and 19.8%, respectively. The three models of STI reported here
represent a significant improvement over the partial inhibitor structure in the
complex, which was previously determined at a nominal resolution of 2.6 A by the
multiple isomorphous replacement method. This study provides the first
high-resolution picture of the complex between a Kunitz-type proteinase
inhibitor with its cognate proteinase. Many of the external loops of STI show
high B-factors, both in the free and the complexed states, except the reactive
site loop whose B-factors are dramatically reduced upon complexation. The
reactive site loop of STI adopts a canonical conformation similar to those in
other substrate-like inhibitors. The P1 carbonyl group displays no out-of-plane
displacement and thus retains a nominal trigonal planar geometry. Modeling
studies on the complex between a homologous Kunitz-type trypsin inhibitor DE-3
from Erythrina caffra and the human tissue-type plasminogen activator reveal a
new insight into the specific interactions which could play a crucial role in
their binding.
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Selected figure(s)
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Figure 5.
Figure 5. Stereo diagram showing the interactions between
the bound water molecule (Wat34) and three β-strands (Aβ3,
Bβ3 and Cβ3). The distances between the water and oxygen atoms
of the inhibitor are given, with a distance too long for a
hydrogen bond in parenthesis.
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Figure 13.
Figure 13. A comparison of molecular surfaces. Positively
charged regions are blue and negatively charged regions red. The
P1 residue, S1 pocket and some basic and acidic patches are
labeled. This figure was generated using GRASP (Nicholls, 1992).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1998,
275,
347-363)
copyright 1998.
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Figures were
selected
by an automated process.
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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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A.M.Ruvinsky,
T.Kirys,
A.V.Tuzikov,
and
I.A.Vakser
(2011).
Side-chain conformational changes upon Protein-Protein Association.
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J Mol Biol,
408,
356-365.
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J.M.Mondego,
M.P.Duarte,
E.Kiyota,
L.Martínez,
S.R.de Camargo,
F.P.De Caroli,
B.S.Alves,
S.M.Guerreiro,
M.L.Oliva,
O.Guerreiro-Filho,
and
M.Menossi
(2011).
Molecular characterization of a miraculin-like gene differentially expressed during coffee development and coffee leaf miner infestation.
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Planta,
233,
123-137.
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B.G.Lee,
E.Y.Park,
K.E.Lee,
H.Jeon,
K.H.Sung,
H.Paulsen,
H.Rübsamen-Schaeff,
H.Brötz-Oesterhelt,
and
H.K.Song
(2010).
Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism.
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Nat Struct Mol Biol,
17,
471-478.
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PDB codes:
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M.Khalf,
C.Goulet,
J.Vorster,
F.Brunelle,
R.Anguenot,
I.Fliss,
and
D.Michaud
(2010).
Tubers from potato lines expressing a tomato Kunitz protease inhibitor are substantially equivalent to parental and transgenic controls.
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Plant Biotechnol J,
8,
155-169.
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M.Renko,
J.Sabotic,
M.Mihelic,
J.Brzin,
J.Kos,
and
D.Turk
(2010).
Versatile loops in mycocypins inhibit three protease families.
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J Biol Chem,
285,
308-316.
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PDB codes:
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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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S.Khamrui,
S.Majumder,
J.Dasgupta,
J.K.Dattagupta,
and
U.Sen
(2010).
Identification of a novel set of scaffolding residues that are instrumental for the inhibitory property of Kunitz (STI) inhibitors.
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Protein Sci,
19,
593-602.
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PDB codes:
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R.Bao,
C.Z.Zhou,
C.Jiang,
S.X.Lin,
C.W.Chi,
and
Y.Chen
(2009).
The ternary structure of the double-headed arrowhead protease inhibitor API-A complexed with two trypsins reveals a novel reactive site conformation.
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J Biol Chem,
284,
26676-26684.
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PDB code:
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R.N.Philippe,
S.G.Ralph,
C.Külheim,
S.I.Jancsik,
and
J.Bohlmann
(2009).
Poplar defense against insects: genome analysis, full-length cDNA cloning, and transcriptome and protein analysis of the poplar Kunitz-type protease inhibitor family.
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New Phytol,
184,
865-884.
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S.Koutsopoulos,
L.D.Unsworth,
Y.Nagai,
and
S.Zhang
(2009).
Controlled release of functional proteins through designer self-assembling peptide nanofiber hydrogel scaffold.
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Proc Natl Acad Sci U S A,
106,
4623-4628.
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C.Jiang,
R.Bao,
and
Y.Chen
(2008).
Expression, purification, crystallization and preliminary X-ray diffraction analysis of Sagittaria sagittifolia arrowhead protease inhibitor API-A in complex with bovine trypsin.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
64,
1060-1062.
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T.Reiner,
S.Kababya,
and
I.Gotman
(2008).
Protein incorporation within Ti scaffold for bone ingrowth using Sol-gel SiO(2) as a slow release carrier.
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J Mater Sci Mater Med,
19,
583-589.
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I.A.Solov'yov,
A.V.Yakubovich,
A.V.Solov'yov,
and
W.Greiner
(2007).
Two-center-multipole expansion method: application to macromolecular systems.
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Phys Rev E Stat Nonlin Soft Matter Phys,
75,
051912.
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A.D.van Dijk,
and
A.M.Bonvin
(2006).
Solvated docking: introducing water into the modelling of biomolecular complexes.
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Bioinformatics,
22,
2340-2347.
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F.J.Milder,
H.C.Raaijmakers,
M.D.Vandeputte,
A.Schouten,
E.G.Huizinga,
R.A.Romijn,
W.Hemrika,
A.Roos,
M.R.Daha,
and
P.Gros
(2006).
Structure of complement component C2A: implications for convertase formation and substrate binding.
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Structure,
14,
1587-1597.
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PDB codes:
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M.Azarkan,
A.Garcia-Pino,
R.Dibiani,
L.Wyns,
R.Loris,
and
D.Baeyens-Volant
(2006).
Crystallization and preliminary X-ray analysis of a protease inhibitor from the latex of Carica papaya.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
62,
1239-1242.
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N.M.Talyzina,
and
P.K.Ingvarsson
(2006).
Molecular evolution of a small gene family of wound inducible Kunitz trypsin inhibitors in Populus.
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J Mol Evol,
63,
108-119.
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Y.Hirano,
M.M.Hossain,
K.Takeda,
H.Tokuda,
and
K.Miki
(2006).
Purification, crystallization and preliminary X-ray crystallographic analysis of the outer membrane lipoprotein NlpE from Escherichia coli.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
62,
1227-1230.
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A.Gutteridge,
and
J.M.Thornton
(2005).
Understanding nature's catalytic toolkit.
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Trends Biochem Sci,
30,
622-629.
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D.Navaneetham,
L.Jin,
P.Pandey,
J.E.Strickler,
R.E.Babine,
S.S.Abdel-Meguid,
and
P.N.Walsh
(2005).
Structural and mutational analyses of the molecular interactions between the catalytic domain of factor XIa and the Kunitz protease inhibitor domain of protease nexin 2.
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J Biol Chem,
280,
36165-36175.
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PDB code:
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D.Segal,
and
M.Eisenstein
(2005).
The effect of resolution-dependent global shape modifications on rigid-body protein-protein docking.
|
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Proteins,
59,
580-591.
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S.Iwanaga,
N.Yamasaki,
M.Kimura,
and
Y.Kouzuma
(2005).
Contribution of conserved Asn residues to the inhibitory activities of Kunitz-type protease inhibitors from plants.
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Biosci Biotechnol Biochem,
69,
220-223.
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Z.Zhu,
Z.Liang,
T.Zhang,
Z.Zhu,
W.Xu,
M.Teng,
and
L.Niu
(2005).
Crystal structures and amidolytic activities of two glycosylated snake venom serine proteinases.
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J Biol Chem,
280,
10524-10529.
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PDB codes:
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A.Berchanski,
B.Shapira,
and
M.Eisenstein
(2004).
Hydrophobic complementarity in protein-protein docking.
|
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Proteins,
56,
130-142.
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A.R.Lopes,
M.A.Juliano,
L.Juliano,
and
W.R.Terra
(2004).
Coevolution of insect trypsins and inhibitors.
|
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Arch Insect Biochem Physiol,
55,
140-152.
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I.Cruz-Silva,
A.J.Gozzo,
V.A.Nunes,
A.K.Carmona,
A.Faljoni-Alario,
M.L.Oliva,
M.U.Sampaio,
C.A.Sampaio,
and
M.S.Araujo
(2004).
A proteinase inhibitor from Caesalpinia echinata (pau-brasil) seeds for plasma kallikrein, plasmin and factor XIIa.
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Biol Chem,
385,
1083-1086.
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L.Prasad,
Y.Leduc,
K.Hayakawa,
and
L.T.Delbaere
(2004).
The structure of a universally employed enzyme: V8 protease from Staphylococcus aureus.
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Acta Crystallogr D Biol Crystallogr,
60,
256-259.
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PDB codes:
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T.Z.Sen,
A.Kloczkowski,
R.L.Jernigan,
C.Yan,
V.Honavar,
K.M.Ho,
C.Z.Wang,
Y.Ihm,
H.Cao,
X.Gu,
and
D.Dobbs
(2004).
Predicting binding sites of hydrolase-inhibitor complexes by combining several methods.
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BMC Bioinformatics,
5,
205.
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I.H.Barrette-Ng,
K.K.Ng,
M.M.Cherney,
G.Pearce,
U.Ghani,
C.A.Ryan,
and
M.N.James
(2003).
Unbound form of tomato inhibitor-II reveals interdomain flexibility and conformational variability in the reactive site loops.
|
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J Biol Chem,
278,
31391-31400.
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PDB code:
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J.R.Bradford,
and
D.R.Westhead
(2003).
Asymmetric mutation rates at enzyme-inhibitor interfaces: implications for the protein-protein docking problem.
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Protein Sci,
12,
2099-2103.
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M.Volpicella,
L.R.Ceci,
J.Cordewener,
T.America,
R.Gallerani,
W.Bode,
M.A.Jongsma,
and
J.Beekwilder
(2003).
Properties of purified gut trypsin from Helicoverpa zea, adapted to proteinase inhibitors.
|
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Eur J Biochem,
270,
10-19.
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A.Heifetz,
E.Katchalski-Katzir,
and
M.Eisenstein
(2002).
Electrostatics in protein-protein docking.
|
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Protein Sci,
11,
571-587.
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O.L.Franco,
M.F.Grossi de Sá,
M.P.Sales,
L.V.Mello,
A.S.Oliveira,
and
D.J.Rigden
(2002).
Overlapping binding sites for trypsin and papain on a Kunitz-type proteinase inhibitor from Prosopis juliflora.
|
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Proteins,
49,
335-341.
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C.Paine,
E.Sharlow,
F.Liebel,
M.Eisinger,
S.Shapiro,
and
M.Seiberg
(2001).
An alternative approach to depigmentation by soybean extracts via inhibition of the PAR-2 pathway.
|
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J Invest Dermatol,
116,
587-595.
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S.R.Brych,
S.I.Blaber,
T.M.Logan,
and
M.Blaber
(2001).
Structure and stability effects of mutations designed to increase the primary sequence symmetry within the core region of a beta-trefoil.
|
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Protein Sci,
10,
2587-2599.
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PDB codes:
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J.K.Dattagupta,
A.Podder,
C.Chakrabarti,
U.Sen,
D.Mukhopadhyay,
S.K.Dutta,
and
M.Singh
(1999).
Refined crystal structure (2.3 A) of a double-headed winged bean alpha-chymotrypsin inhibitor and location of its second reactive site.
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Proteins,
35,
321-331.
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PDB code:
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S.Ravichandran,
U.Sen,
C.Chakrabarti,
and
J.K.Dattagupta
(1999).
Cryocrystallography of a Kunitz-type serine protease inhibitor: the 90 K structure of winged bean chymotrypsin inhibitor (WCI) at 2.13 A resolution.
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Acta Crystallogr D Biol Crystallogr,
55,
1814-1821.
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PDB code:
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T.Kishi,
M.Kato,
T.Shimizu,
K.Kato,
K.Matsumoto,
S.Yoshida,
S.Shiosaka,
and
T.Hakoshima
(1999).
Crystal structure of neuropsin, a hippocampal protease involved in kindling epileptogenesis.
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J Biol Chem,
274,
4220-4224.
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PDB code:
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V.Y.Hook,
C.Sei,
S.Yasothornsrikul,
T.Toneff,
Y.H.Kang,
S.Efthimiopoulos,
N.K.Robakis,
and
W.Van Nostrand
(1999).
The kunitz protease inhibitor form of the amyloid precursor protein (KPI/APP) inhibits the proneuropeptide processing enzyme prohormone thiol protease (PTP). Colocalization of KPI/APP and PTP in secretory vesicles.
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J Biol Chem,
274,
3165-3172.
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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
