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Publication Abstract from PubMed

P-glycoprotein (P-gp) is a polyspecific ATP-dependent transporter linked to multidrug resistance in cancers that plays important roles in the pharmacokinetics of a large number of drugs. The drug-resistance phenotype of P-gp can be modulated by the monoclonal antibody UIC2, which specifically recognizes human P-gp in a conformation-dependent manner. Here, the purification, sequence determination and high-resolution structure of the Fab fragment of UIC2 (UIC2/Fab) are reported. Purified UIC2/Fab binds human P-gp with a 1:1 stoichiometry. Crystals of UIC2/Fab are triclinic (space group P1), with unit-cell parameters a = 40.67, b = 44.91, c = 58.09 A, alpha = 97.62, beta = 99.10, gamma = 94.09 degrees , and diffracted X-rays to 1.6 A resolution. The structure was determined by molecular replacement and refined to 1.65 A resolution. The asymmetric unit contains one molecule of UIC2/Fab, which exhibits a positively charged antigen-binding surface, suggesting that it might recognize an oppositely charged extracellular epitope of P-gp.

Crystal structure of the antigen-binding fragment of a monoclonal antibody specific for the multidrug-resistance-linked ABC transporter human P-glycoprotein.,Esser L, Shukla S, Zhou F, Ambudkar SV, Xia D Acta Crystallogr F Struct Biol Commun. 2016 Aug;72(Pt 8):636-41. doi:, 10.1107/S2053230X16009778. Epub 2016 Jul 27. PMID:27487928^[1]

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