6fvh

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Macrophage Migration Inhibitory Factor (MIF) with Covalently Bound PITC

Structural highlights

6fvh is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:0FI, SO4
Gene:MIF, GLIF, MMIF (HUMAN)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MIF_HUMAN] Genetic variations in MIF are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]. An inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis.

Function

[MIF_HUMAN] Pro-inflammatory cytokine. Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity.[1] [2]

Publication Abstract from PubMed

Macrophage migration inhibitory factor (MIF) is a key proinflammatory cytokine. Inhibitors of tautomerase activity of MIF are perspective antiinflammatory compounds. Ceruloplasmin, the copper-containing ferroxidase of blood plasma, is a noncompetitive inhibitor of tautomerase activity of MIF in the reaction with p-hydroxyphenylpyruvate. Small-angle X-ray scattering established a model of the complex formed by MIF and ceruloplasmin. Crystallographic analysis of MIF with a modified active site supports the model. The stoichiometry of 3 CP/MIF trimer complex was established using gel filtration. Conformity of novel data concerning the interaction regions in the studied proteins with previous biochemical data is discussed.

Structural Study of the Complex Formed by Ceruloplasmin and Macrophage Migration Inhibitory Factor.,Sokolov AV, Dadinova LA, Petoukhov MV, Bourenkov G, Dubova KM, Amarantov SV, Volkov VV, Kostevich VA, Gorbunov NP, Grudinina NA, Vasilyev VB, Samygina VR Biochemistry (Mosc). 2018 Jun;83(6):701-707. doi: 10.1134/S000629791806007X. PMID:30195326[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. Oddo M, Calandra T, Bucala R, Meylan PR. Macrophage migration inhibitory factor reduces the growth of virulent Mycobacterium tuberculosis in human macrophages. Infect Immun. 2005 Jun;73(6):3783-6. PMID:15908412 doi:10.1128/IAI.73.6.3783-3786.2005
  2. Emonts M, Sweep FC, Grebenchtchikov N, Geurts-Moespot A, Knaup M, Chanson AL, Erard V, Renner P, Hermans PW, Hazelzet JA, Calandra T. Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis. Clin Infect Dis. 2007 May 15;44(10):1321-8. Epub 2007 Apr 5. PMID:17443469 doi:10.1086/514344
  3. Sokolov AV, Dadinova LA, Petoukhov MV, Bourenkov G, Dubova KM, Amarantov SV, Volkov VV, Kostevich VA, Gorbunov NP, Grudinina NA, Vasilyev VB, Samygina VR. Structural Study of the Complex Formed by Ceruloplasmin and Macrophage Migration Inhibitory Factor. Biochemistry (Mosc). 2018 Jun;83(6):701-707. doi: 10.1134/S000629791806007X. PMID:30195326 doi:http://dx.doi.org/10.1134/S000629791806007X

Contents


6fvh, resolution 1.40Å

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