5JUE

Crystal Structure of UIC2 Fab

Summary for 5JUE

• Entry DOI: 10.2210/pdb5jue/pdb
• Descriptor: light chain of UIC2 Fab, heavy chain of UIC2 Fab, GLYCEROL, ... (4 entities in total)
• Functional Keywords: antibody fab, p-glycoprotein, transport inhibition, immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 2
• Total formula weight: 49028.62

Authors

Xia, D.,Esser, L. (deposition date: 2016-05-10, release date: 2016-08-31, Last modification date: 2024-11-06)

Primary citation

Esser, L.,Shukla, S.,Zhou, F.,Ambudkar, S.V.,Xia, D.
Crystal structure of the antigen-binding fragment of a monoclonal antibody specific for the multidrug-resistance-linked ABC transporter human P-glycoprotein.
Acta Crystallogr.,Sect.F, 72:636-641, 2016

PubMed Abstract: 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 Å, α = 97.62, β = 99.10, γ = 94.09°, and diffracted X-rays to 1.6 Å resolution. The structure was determined by molecular replacement and refined to 1.65 Å 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.

PubMed: 27487928
DOI: 10.1107/S2053230X16009778

Experimental method

X-RAY DIFFRACTION (1.65 Å)