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PDBsum entry 1mif
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Contents |
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* Residue conservation analysis
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Enzyme class 2:
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E.C.5.3.2.1
- phenylpyruvate tautomerase.
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Reaction:
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3-phenylpyruvate = enol-phenylpyruvate
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3-phenylpyruvate
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=
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enol-phenylpyruvate
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Enzyme class 3:
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E.C.5.3.3.12
- L-dopachrome isomerase.
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Pathway:
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Reaction:
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L-dopachrome = 5,6-dihydroxyindole-2-carboxylate
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L-dopachrome
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=
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5,6-dihydroxyindole-2-carboxylate
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Cofactor:
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Zn(2+)
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Proc Natl Acad Sci U S A
93:5191-5196
(1996)
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PubMed id:
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Crystal structure at 2.6-A resolution of human macrophage migration inhibitory factor.
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H.W.Sun,
J.Bernhagen,
R.Bucala,
E.Lolis.
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ABSTRACT
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Macrophage migration inhibitory factor (MIF) was the first cytokine to be
described, but for 30 years its role in the immune response remained enigmatic.
In recent studies, MIF has been found to be a novel pituitary hormone and the
first protein identified to be released from immune cells on glucocorticoid
stimulation. Once secreted, MIF counterregulates the immunosuppressive effects
of steroids and thus acts as a critical component of the immune system to
control both local and systemic immune responses. We report herein the x-ray
crystal structure of human MIF to 2.6 angstrom resolution. The protein is a
trimer of identical subunits. Each monomer contains two antiparallel
alpha-helices that pack against a four-stranded beta-sheet. The monomer has an
additional two beta-strands that interact with the beta-sheets of adjacent
subunits to form the interface between monomers. The three beta-sheets are
arranged to form a barrel containing a solvent-accessible channel that runs
through the center of the protein along a molecular 3-fold axis. Electrostatic
potential maps reveal that the channel has a positive potential, suggesting that
it binds negatively charged molecules. The elucidated structure for MIF is
unique among cytokines or hormonal mediators, and suggests that this
counterregulator of glucocorticoid action participates in novel ligand-receptor
interactions.
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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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F.Li,
S.Huang,
L.Wang,
J.Yang,
H.Zhang,
L.Qiu,
L.Li,
and
L.Song
(2011).
A macrophage migration inhibitory factor like gene from scallop Chlamys farreri: Involvement in immune response and wound healing.
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Dev Comp Immunol,
35,
62-71.
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H.Conroy,
L.Mawhinney,
and
S.C.Donnelly
(2010).
Inflammation and cancer: macrophage migration inhibitory factor (MIF)--the potential missing link.
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QJM,
103,
831-836.
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H.Kimura,
Y.Sato,
Y.Tajima,
H.Suzuki,
H.Yukitake,
T.Imaeda,
M.Kajino,
H.Oki,
M.Takizawa,
and
S.Tanida
(2010).
BTZO-1, a cardioprotective agent, reveals that macrophage migration inhibitory factor regulates ARE-mediated gene expression.
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Chem Biol,
17,
1282-1294.
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PDB code:
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Y.Cho,
G.V.Crichlow,
J.J.Vermeire,
L.Leng,
X.Du,
M.E.Hodsdon,
R.Bucala,
M.Cappello,
M.Gross,
F.Gaeta,
K.Johnson,
and
E.J.Lolis
(2010).
Allosteric inhibition of macrophage migration inhibitory factor revealed by ibudilast.
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Proc Natl Acad Sci U S A,
107,
11313-11318.
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PDB codes:
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A.Son,
N.Kato,
T.Horibe,
Y.Matsuo,
M.Mochizuki,
A.Mitsui,
K.Kawakami,
H.Nakamura,
and
J.Yodoi
(2009).
Direct association of thioredoxin-1 (TRX) with macrophage migration inhibitory factor (MIF): regulatory role of TRX on MIF internalization and signaling.
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Antioxid Redox Signal,
11,
2595-2605.
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B.E.Rendon,
S.S.Willer,
W.Zundel,
and
R.A.Mitchell
(2009).
Mechanisms of macrophage migration inhibitory factor (MIF)-dependent tumor microenvironmental adaptation.
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Exp Mol Pathol,
86,
180-185.
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G.Fingerle-Rowson,
D.R.Kaleswarapu,
C.Schlander,
N.Kabgani,
T.Brocks,
N.Reinart,
R.Busch,
A.Schütz,
H.Lue,
X.Du,
A.Liu,
H.Xiong,
Y.Chen,
A.Nemajerova,
M.Hallek,
J.Bernhagen,
L.Leng,
and
R.Bucala
(2009).
A tautomerase-null macrophage migration-inhibitory factor (MIF) gene knock-in mouse model reveals that protein interactions and not enzymatic activity mediate MIF-dependent growth regulation.
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Mol Cell Biol,
29,
1922-1932.
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S.E.Dobson,
K.D.Augustijn,
J.A.Brannigan,
C.Schnick,
C.J.Janse,
E.J.Dodson,
A.P.Waters,
and
A.J.Wilkinson
(2009).
The crystal structures of macrophage migration inhibitory factor from Plasmodium falciparum and Plasmodium berghei.
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Protein Sci,
18,
2578-2591.
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PDB codes:
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Z.Cournia,
L.Leng,
S.Gandavadi,
X.Du,
R.Bucala,
and
W.L.Jorgensen
(2009).
Discovery of human macrophage migration inhibitory factor (MIF)-CD74 antagonists via virtual screening.
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J Med Chem,
52,
416-424.
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A.M.Coleman,
B.E.Rendon,
M.Zhao,
M.W.Qian,
R.Bucala,
D.Xin,
and
R.A.Mitchell
(2008).
Cooperative regulation of non-small cell lung carcinoma angiogenic potential by macrophage migration inhibitory factor and its homolog, D-dopachrome tautomerase.
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J Immunol,
181,
2330-2337.
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A.Schober,
J.Bernhagen,
and
C.Weber
(2008).
Chemokine-like functions of MIF in atherosclerosis.
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J Mol Med,
86,
761-770.
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C.Toso,
J.A.Emamaullee,
S.Merani,
and
A.M.Shapiro
(2008).
The role of macrophage migration inhibitory factor on glucose metabolism and diabetes.
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Diabetologia,
51,
1937-1946.
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C.Weber,
S.Kraemer,
M.Drechsler,
H.Lue,
R.R.Koenen,
A.Kapurniotu,
A.Zernecke,
and
J.Bernhagen
(2008).
Structural determinants of MIF functions in CXCR2-mediated inflammatory and atherogenic leukocyte recruitment.
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Proc Natl Acad Sci U S A,
105,
16278-16283.
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D.Kamir,
S.Zierow,
L.Leng,
Y.Cho,
Y.Diaz,
J.Griffith,
C.McDonald,
M.Merk,
R.A.Mitchell,
J.Trent,
Y.Chen,
Y.K.Kwong,
H.Xiong,
J.Vermeire,
M.Cappello,
D.McMahon-Pratt,
J.Walker,
J.Bernhagen,
E.Lolis,
and
R.Bucala
(2008).
A Leishmania ortholog of macrophage migration inhibitory factor modulates host macrophage responses.
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J Immunol,
180,
8250-8261.
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PDB code:
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G.J.Poelarends,
V.P.Veetil,
and
C.P.Whitman
(2008).
The chemical versatility of the beta-alpha-beta fold: catalytic promiscuity and divergent evolution in the tautomerase superfamily.
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Cell Mol Life Sci,
65,
3606-3618.
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M.Winner,
J.Meier,
S.Zierow,
B.E.Rendon,
G.V.Crichlow,
R.Riggs,
R.Bucala,
L.Leng,
N.Smith,
E.Lolis,
J.O.Trent,
and
R.A.Mitchell
(2008).
A novel, macrophage migration inhibitory factor suicide substrate inhibits motility and growth of lung cancer cells.
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Cancer Res,
68,
7253-7257.
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PDB code:
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G.J.Poelarends,
W.H.Johnson,
H.Serrano,
and
C.P.Whitman
(2007).
Phenylpyruvate tautomerase activity of trans-3-chloroacrylic acid dehalogenase: evidence for an enol intermediate in the dehalogenase reaction?
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Biochemistry,
46,
9596-9604.
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H.Lue,
M.Thiele,
J.Franz,
E.Dahl,
S.Speckgens,
L.Leng,
G.Fingerle-Rowson,
R.Bucala,
B.Lüscher,
and
J.Bernhagen
(2007).
Macrophage migration inhibitory factor (MIF) promotes cell survival by activation of the Akt pathway and role for CSN5/JAB1 in the control of autocrine MIF activity.
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Oncogene,
26,
5046-5059.
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J.Bernhagen,
R.Krohn,
H.Lue,
J.L.Gregory,
A.Zernecke,
R.R.Koenen,
M.Dewor,
I.Georgiev,
A.Schober,
L.Leng,
T.Kooistra,
G.Fingerle-Rowson,
P.Ghezzi,
R.Kleemann,
S.R.McColl,
R.Bucala,
M.J.Hickey,
and
C.Weber
(2007).
MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment.
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Nat Med,
13,
587-596.
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J.M.Kneller,
T.Ehlen,
J.P.Matisic,
D.Miller,
D.Van Niekerk,
W.L.Lam,
M.Marra,
R.Richards-Kortum,
M.Follen,
C.Macaulay,
and
S.J.Jones
(2007).
Using LongSAGE to Detect Biomarkers of Cervical Cancer Potentially Amenable to Optical Contrast Agent Labelling.
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Biomark Insights,
2,
447-461.
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P.Viganò,
M.Cintorino,
F.Schatz,
C.J.Lockwood,
and
F.Arcuri
(2007).
The role of macrophage migration inhibitory factor in maintaining the immune privilege at the fetal-maternal interface.
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Semin Immunopathol,
29,
135-150.
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R.Sullivan,
G.Frenette,
and
J.Girouard
(2007).
Epididymosomes are involved in the acquisition of new sperm proteins during epididymal transit.
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Asian J Androl,
9,
483-491.
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T.Sakuragi,
X.Lin,
C.N.Metz,
K.Ojamaa,
N.Kohn,
Y.Al-Abed,
and
E.J.Miller
(2007).
Lung-derived macrophage migration inhibitory factor in sepsis induces cardio-circulatory depression.
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Surg Infect (Larchmt),
8,
29-40.
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L.Leng,
and
R.Bucala
(2006).
Insight into the biology of macrophage migration inhibitory factor (MIF) revealed by the cloning of its cell surface receptor.
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Cell Res,
16,
162-168.
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O.A.Cherepkova,
E.M.Lyutova,
and
B.Y.Gurvits
(2006).
Macrophage migration inhibitory factor: isolation from bovine brain.
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Biochemistry (Mosc),
71,
73-78.
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O.A.Cherepkova,
E.M.Lyutova,
T.B.Eronina,
and
B.Y.Gurvits
(2006).
Chaperone-like activity of macrophage migration inhibitory factor.
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Int J Biochem Cell Biol,
38,
43-55.
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P.L.Vera,
and
K.L.Meyer-Siegler
(2006).
Substance P induces localization of MIF/alpha1-inhibitor-3 complexes to umbrella cells via paracellular transit through the urothelium in the rat bladder.
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BMC Urol,
6,
24.
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K.L.Meyer-Siegler,
K.A.Iczkowski,
and
P.L.Vera
(2005).
Further evidence for increased macrophage migration inhibitory factor expression in prostate cancer.
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BMC Cancer,
5,
73.
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M.Thiele,
and
J.Bernhagen
(2005).
Link between macrophage migration inhibitory factor and cellular redox regulation.
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Antioxid Redox Signal,
7,
1234-1248.
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O.A.Cherepkova,
E.M.Lutova,
and
B.Y.Gurvits
(2005).
Charge heterogeneity of bovine brain macrophage migration inhibitory factor.
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Neurochem Res,
30,
151-158.
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P.L.Vera,
K.A.Iczkowski,
L.Leng,
R.Bucala,
and
K.L.Meyer-Siegler
(2005).
Macrophage migration inhibitory factor is released as a complex with alpha1-inhibitor-3 in the intraluminal fluid during bladder inflammation in the rat.
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J Urol,
174,
338-343.
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P.Renner,
T.Roger,
and
T.Calandra
(2005).
Macrophage migration inhibitory factor: gene polymorphisms and susceptibility to inflammatory diseases.
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Clin Infect Dis,
41,
S513-S519.
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R.Sullivan,
F.Saez,
J.Girouard,
and
G.Frenette
(2005).
Role of exosomes in sperm maturation during the transit along the male reproductive tract.
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Blood Cells Mol Dis,
35,
1.
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E.Lolis,
and
R.Bucala
(2003).
Therapeutic approaches to innate immunity: severe sepsis and septic shock.
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Nat Rev Drug Discov,
2,
635-645.
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E.Lolis,
and
R.Bucala
(2003).
Macrophage migration inhibitory factor.
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Expert Opin Ther Targets,
7,
153-164.
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T.Calandra,
C.Froidevaux,
C.Martin,
and
T.Roger
(2003).
Macrophage migration inhibitory factor and host innate immune defenses against bacterial sepsis.
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J Infect Dis,
187,
S385-S390.
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T.Calandra,
and
T.Roger
(2003).
Macrophage migration inhibitory factor: a regulator of innate immunity.
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Nat Rev Immunol,
3,
791-800.
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J.A.Baugh,
and
R.Bucala
(2002).
Macrophage migration inhibitory factor.
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Crit Care Med,
30,
S27-S35.
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P.D.Senter,
Y.Al-Abed,
C.N.Metz,
F.Benigni,
R.A.Mitchell,
J.Chesney,
J.Han,
C.G.Gartner,
S.D.Nelson,
G.J.Todaro,
and
R.Bucala
(2002).
Inhibition of macrophage migration inhibitory factor (MIF) tautomerase and biological activities by acetaminophen metabolites.
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Proc Natl Acad Sci U S A,
99,
144-149.
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R.Kleemann,
M.Grell,
R.Mischke,
G.Zimmermann,
and
J.Bernhagen
(2002).
Receptor binding and cellular uptake studies of macrophage migration inhibitory factor (MIF): use of biologically active labeled MIF derivatives.
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J Interferon Cytokine Res,
22,
351-363.
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T.A.Soares,
R.D.Lins,
T.P.Straatsma,
and
J.M.Briggs
(2002).
Internal dynamics and ionization states of the macrophage migration inhibitory factor: comparison between wild-type and mutant forms.
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Biopolymers,
65,
313-323.
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R.Kleemann,
H.Rorsman,
E.Rosengren,
R.Mischke,
N.T.Mai,
and
J.Bernhagen
(2000).
Dissection of the enzymatic and immunologic functions of macrophage migration inhibitory factor. Full immunologic activity of N-terminally truncated mutants.
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Eur J Biochem,
267,
7183-7193.
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T.Soares,
D.Goodsell,
R.Ferreira,
A.J.Olson,
and
J.M.Briggs
(2000).
Ionization state and molecular docking studies for the macrophage migration inhibitory factor: the role of lysine 32 in the catalytic mechanism.
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J Mol Recognit,
13,
146-156.
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A.B.Taylor,
W.H.Johnson,
R.M.Czerwinski,
H.S.Li,
M.L.Hackert,
and
C.P.Whitman
(1999).
Crystal structure of macrophage migration inhibitory factor complexed with (E)-2-fluoro-p-hydroxycinnamate at 1.8 A resolution: implications for enzymatic catalysis and inhibition.
|
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Biochemistry,
38,
7444-7452.
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PDB code:
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E.O.Long
(1999).
Regulation of immune responses through inhibitory receptors.
|
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Annu Rev Immunol,
17,
875-904.
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E.Zerovnik,
V.Janjić,
A.Francky,
and
B.Mozetic-Francky
(1999).
Equilibrium and transient intermediates in folding of human macrophage migration inhibitory factor.
|
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Eur J Biochem,
260,
609-618.
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G.K.Farber
(1999).
New approaches to rational drug design.
|
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Pharmacol Ther,
84,
327-332.
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J.B.Lubetsky,
M.Swope,
C.Dealwis,
P.Blake,
and
E.Lolis
(1999).
Pro-1 of macrophage migration inhibitory factor functions as a catalytic base in the phenylpyruvate tautomerase activity.
|
| |
Biochemistry,
38,
7346-7354.
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PDB codes:
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J.Chesney,
C.Metz,
M.Bacher,
T.Peng,
A.Meinhardt,
and
R.Bucala
(1999).
An essential role for macrophage migration inhibitory factor (MIF) in angiogenesis and the growth of a murine lymphoma.
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Mol Med,
5,
181-191.
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R.Kleemann,
A.Kapurniotu,
R.Mischke,
J.Held,
and
J.Bernhagen
(1999).
Characterization of catalytic centre mutants of macrophage migration inhibitory factor (MIF) and comparison to Cys81Ser MIF.
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Eur J Biochem,
261,
753-766.
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D.V.Pastrana,
N.Raghavan,
P.FitzGerald,
S.W.Eisinger,
C.Metz,
R.Bucala,
R.P.Schleimer,
C.Bickel,
and
A.L.Scott
(1998).
Filarial nematode parasites secrete a homologue of the human cytokine macrophage migration inhibitory factor.
|
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Infect Immun,
66,
5955-5963.
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M.Swope,
H.W.Sun,
P.R.Blake,
and
E.Lolis
(1998).
Direct link between cytokine activity and a catalytic site for macrophage migration inhibitory factor.
|
| |
EMBO J,
17,
3534-3541.
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R.Bucala
(1998).
Neuroimmunomodulation by macrophage migration inhibitory factor (MIF).
|
| |
Ann N Y Acad Sci,
840,
74-82.
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S.L.Stamps,
M.C.Fitzgerald,
and
C.P.Whitman
(1998).
Characterization of the role of the amino-terminal proline in the enzymatic activity catalyzed by macrophage migration inhibitory factor.
|
| |
Biochemistry,
37,
10195-10202.
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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
