6c0v

Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation

spinqualitylabelsall models 6c0v, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6c0v is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ATP, MG Gene: ABCB1, MDR1, PGY1 (HUMAN) Activity: Xenobiotic-transporting ATPase, with EC number 3.6.3.44 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [MDR1_HUMAN] Ulcerative colitis. Disease susceptibility is associated with variations affecting the gene represented in this entry. Function [MDR1_HUMAN] Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells. Publication Abstract from PubMed The multidrug transporter P-glycoprotein is an ATP-binding cassette exporter responsible for clinical resistance to chemotherapy. P-glycoprotein extrudes toxic molecules and drugs from cells through ATP-powered conformational changes. Despite decades of effort, only the structures of the inward-facing conformation of P-glycoprotein are available. Here we present the structure of human P-glycoprotein in the outward-facing conformation, determined by electron cryo-microscopy at 3.4-A resolution. The two nucleotide-binding domains form a closed dimer occluding two ATP molecules. The drug-binding cavity observed in the inward-facing structures is re-orientated toward the extracellular space and compressed to preclude substrate binding. This observation indicates that ATP binding, not hydrolysis, promotes substrate release. The structure evokes a model in which the dynamic nature of P-glycoprotein enables translocation of a large variety of substrates. Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation.,Kim Y, Chen J Science. 2018 Jan 25. pii: science.aar7389. doi: 10.1126/science.aar7389. PMID:29371429 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA