3wmg

Crystal structure of an inward-facing eukaryotic ABC multidrug transporter G277V/A278V/A279V mutant in complex with an cyclic peptide inhibitor, aCAP

spinqualitylabelsall models 3wmg, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3wmg is a 2 chain structure. Full crystallographic information is available from OCA. Related: 3wme, 3wmf Activity: Glucokinase, with EC number 2.7.1.2 Publication Abstract from PubMed P-glycoprotein is an ATP-binding cassette multidrug transporter that actively transports chemically diverse substrates across the lipid bilayer. The precise molecular mechanism underlying transport is not fully understood. Here, we present crystal structures of a eukaryotic P-glycoprotein homolog, CmABCB1 from Cyanidioschyzon merolae, in two forms: unbound at 2.6-A resolution and bound to a unique allosteric inhibitor at 2.4-A resolution. The inhibitor clamps the transmembrane helices from the outside, fixing the CmABCB1 structure in an inward-open conformation similar to the unbound structure, confirming that an outward-opening motion is required for ATP hydrolysis cycle. These structures, along with site-directed mutagenesis and transporter activity measurements, reveal the detailed architecture of the transporter, including a gate that opens to extracellular side and two gates that open to intramembranous region and the cytosolic side. We propose that the motion of the nucleotide-binding domain drives those gating apparatuses via two short intracellular helices, IH1 and IH2, and two transmembrane helices, TM2 and TM5. Structural basis for gating mechanisms of a eukaryotic P-glycoprotein homolog.,Kodan A, Yamaguchi T, Nakatsu T, Sakiyama K, Hipolito CJ, Fujioka A, Hirokane R, Ikeguchi K, Watanabe B, Hiratake J, Kimura Y, Suga H, Ueda K, Kato H Proc Natl Acad Sci U S A. 2014 Mar 3. PMID:24591620 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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