4cni

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Crystal structure of the Fab portion of Olokizumab in complex with IL- 6

Structural highlights

4cni is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:SO4, TAM
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

IL6_HUMAN Genetic variations in IL6 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. Note=A IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in HIV-infected men.

Function

IL6_HUMAN Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Involved in lymphocyte and monocyte differentiation. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance.

Publication Abstract from PubMed

Interleukin-6 (IL-6) is a critical regulator of the immune system and has been widely implicated in autoimmune disease. Here, we describe the discovery and characterization of olokizumab, a humanized antibody to IL-6. Data from structural biology, cell biology and primate pharmacology demonstrate the therapeutic potential of targeting IL-6 at "Site 3", blocking the interaction with the signaling co-receptor gp130.

Discovery and characterization of olokizumab: A humanized antibody targeting interleukin-6 and neutralizing gp130-signaling.,Shaw S, Bourne T, Meier C, Carrington B, Gelinas R, Henry A, Popplewell A, Adams R, Baker T, Rapecki S, Marshall D, Moore A, Neale H, Lawson A MAbs. 2014 May 1;6(3):773-81. doi: 10.4161/mabs.28612. Epub 2014 Apr 2. PMID:24670876[1]

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

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See Also

References

  1. Shaw S, Bourne T, Meier C, Carrington B, Gelinas R, Henry A, Popplewell A, Adams R, Baker T, Rapecki S, Marshall D, Moore A, Neale H, Lawson A. Discovery and characterization of olokizumab: A humanized antibody targeting interleukin-6 and neutralizing gp130-signaling. MAbs. 2014 May 1;6(3):773-81. doi: 10.4161/mabs.28612. Epub 2014 Apr 2. PMID:24670876 doi:http://dx.doi.org/10.4161/mabs.28612

Contents


PDB ID 4cni

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