Understanding polyspecificity of multidrug ABC transporters: closing in on the gaps in ABCB1.

ABSTRACT: Multidrug ABC transporters can transport a wide range of drugs from the cell. Ongoing studies of the prototype mammalian multidrug resistance ATP-binding cassette transporter P-glycoprotein (ABCB1) have revealed many intriguing functional and biochemical features. However, a gap remains in our knowledge regarding the molecular basis of its broad specificity for structurally unrelated ligands. Recently, the first crystal structures of ligand-free and ligand-bound ABCB1 showed ligand binding in a cavity between its two membrane domains, and earlier observations on polyspecificity can now be interpreted in a structural context. Comparison of the new ABCB1 crystal structures with structures of bacterial homologs suggests a critical role for an axial rotation of transmembrane helices for high-a

SUBMITTER: Gutmann DA 

PROVIDER: S-EPMC4608440 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature