5az2

Crystal structure of the Fab fragment of 9E5, a murine monoclonal antibody specific for human epiregulin

spinqualitylabelsall models 5az2, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5az2 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Epiregulin (EPR) is a ligand of the epidermal growth factor (EGF) family that upon binding to its epidermal growth factor receptor (EGFR) stimulates proliferative signaling, especially in colon cancer cells. Here, we describe the three-dimensional structure of the EPR antibody (the 9E5(Fab) fragment) in the presence and absence of EPR. Among the six complementarity-determining regions (CDRs), CDR1-3 in the light chain and CDR2 in the heavy chain predominantly recognize EPR. In particular, CDR3 in the heavy chain dramatically moves with cis-trans isomerization of Pro103. A molecular dynamics simulation and mutational analyses revealed that Arg40 in EPR is a key residue for the specific binding of 9E5 IgG. From ITC analysis, the dissociation constant is determined to be 6.5 nM. Surface plasmon resonance analysis revealed that the dissociation rate of 9E5 IgG is extremely slow. The superimposed structure of 9E5(Fab)-EPR on the known complex structure of EGF-EGFR showed that the 9E5(Fab) paratope overlaps with Domains I and III on the EGFR, which reveals that the 9E5(Fab)-EPR complex could not bind to the EGFR. The 9E5 antibody will also be useful in medicine as a neutralizing antibody specific for colon cancer. Epiregulin Recognition Mechanisms by Anti-Epiregulin Antibody 9E5: Structural, Functional and Molecular Dynamics Simulation Analyses.,Kado Y, Mizohata E, Nagatoishi S, Iijima M, Shinoda K, Miyafusa T, Nakayama T, Yoshizumi T, Sugiyama A, Kawamura T, Lee YH, Matsumura H, Doi H, Fujitani H, Kodama T, Shibasaki Y, Tsumoto K, Inoue T J Biol Chem. 2015 Dec 1. pii: jbc.M115.656009. PMID:26627827 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures Sandbox 20009 3D structures of non-human antibody

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