5vh4

Crystal structure of Fab fragment of anti-TNFa antibody infliximab in an I-centered orthorhombic crystal form

spinqualitylabelsall models 5vh4, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5vh4 is a 4 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 2Å Ligands: EDO, NAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Aggregation and self-association in protein-based biotherapeutics are critical quality attributes that are tightly controlled by the manufacturing process. Aggregates have the potential to elicit immune reactions, including neutralizing anti-drug antibodies, which can diminish the drug's efficacy upon subsequent dosing. The structural basis of reversible self-association, a form of non-covalent aggregation in the native state, is only beginning to emerge for many biologics and is often unique to a given molecule. In the present study, crystal structures of the infliximab (Remicade) Fc and Fab domains were determined. The Fab domain structures are the first to be reported in the absence of the antigen (i.e., tumor necrosis factor), and are consistent with a mostly rigid complementarity-determining region loop structure and rotational flexibility between variable and constant regions. A potential self-association interface is conserved in two distinct crystal forms of the Fab domain, and solution studies further demonstrate that reversible self-association of infliximab is mediated by the Fab domain. The crystal structures and corresponding solution studies help rationalize the propensity for infliximab to self-associate and provide insights for the design of improved control strategies in biotherapeutics development. Infliximab crystal structures reveal insights into self-association.,Lerch TF, Sharpe P, Mayclin SJ, Edwards TE, Lee E, Conlon HD, Polleck S, Rouse JC, Luo Y, Zou Q MAbs. 2017 Apr 19:0. doi: 10.1080/19420862.2017.1320463. PMID:28421849 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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