5k64 | pdb_00005k64

Crystal structure of VEGF binding IgG1-Fc (Fcab 448)

spinqualitylabelsall models 5k64, resolution 2.44Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5k64 is a 2 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 2.44Å Ligands: BMA, GOL, MAN, MES, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease IGHG1_HUMAN Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:254500. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4. Function IGHG1_HUMAN Publication Abstract from PubMed Fcabs (Fc domain with antigen-binding sites) are promising novel therapeutics. By engineering of the C-terminal loops of the CH3 domains, two antigen binding sites can be inserted in close proximity. In order to elucidate the binding mode(s) between homodimeric Fcabs and small homodimeric antigens, the interaction between the Fcabs 448 and CT6 (having the AB, CD and EF loops and the C-termini engineered) with homodimeric VEGF was investigated. The crystal structures of these Fcabs, which form polymers with the antigen VEGF in solution, were determined. However, construction of heterodimeric Fcabs (JanusFcabs: one chain Fc-wt, one chain VEGF-binding) results in formation of distinct JanusFcab-VEGF complexes (2:1), which allowed elucidation of the crystal structure of the JanusCT6-VEGF complex at 2.15 A resolution. VEGF binding to Janus448 and JanusCT6 is shown to be entropically unfavorable, but enthalpically favorable. Structure-function relationships are discussed with respect to Fcab design and engineering strategies. Two-Faced Fcab Prevents Polymerization with VEGF and Reveals Thermodynamics and the 2.15 A Crystal Structure of the Complex.,Lobner E, Humm AS, Mlynek G, Kubinger K, Kitzmuller M, Traxlmayr MW, Djinovic-Carugo K, Obinger C MAbs. 2017 Aug 17:0. doi: 10.1080/19420862.2017.1364825. PMID:28816592 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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