3mcl | pdb_00003mcl

Anti-beta-amyloid antibody c706 fab in space group P21

spinqualitylabelsall models 3mcl, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3mcl is a 2 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Ligands: PCA 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 Alzheimer's disease is a progressive neurodegenerative disease characterized by extracellular deposits of beta-amyloid (Abeta) plaques. Aggregation of the Abeta(42) peptide leading to plaque formation is believed to play a central role in Alzheimer's disease pathogenesis. Anti-Abeta monoclonal antibodies can reduce amyloid plaques and could possibly be used for immunotherapy. We have developed a monoclonal antibody C706, which recognizes the human Abeta peptide. Here we report the crystal structure of the antibody Fab fragment at 1.7 A resolution. The structure was determined in two crystal forms, P2(1) and C2. Although the Fab was crystallized in the presence of Abeta(16), no peptide was observed in the crystals. The antigen-binding site is blocked by the hexahistidine tag of another Fab molecule in both crystal forms. The poly-His peptide in an extended conformation occupies a crevice between the light and heavy chains of the variable domain. Two consecutive histidines (His4-His5) stack against tryptophan residues in the central pocket of the antigen-binding surface. In addition, they form hydrogen bonds to the acidic residues at the bottom of the pocket. The mode of his-tag binding by C706 resembles the Abeta recognition by antibodies PFA1 and WO2. All three antibodies recognize the same immunodominant B-cell epitope of Abeta. By similarity, residues Phe-Arg-His of Abeta would be a major portion of the C706 epitope. Copyright (c) 2010 John Wiley & Sons, Ltd. His-tag binding by antibody C706 mimics beta-amyloid recognition.,Teplyakov A, Obmolova G, Canziani G, Zhao Y, Gutshall L, Jung SS, Gilliland GL J Mol Recognit. 2010 Sep 14. PMID:20842634 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA