3wmg
From Proteopedia
(Difference between revisions)
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<StructureSection load='3wmg' size='340' side='right' caption='[[3wmg]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='3wmg' size='340' side='right' caption='[[3wmg]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | [[3wmg]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WMG OCA]. <br> | + | <table><tr><td colspan='2'>[[3wmg]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WMG OCA]. <br> |
| - | <b>[[Ligand|Ligands:]]</b> <scene name='pdbligand=DMU:DECYL-BETA-D-MALTOPYRANOSIDE'>DMU</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene><br> | + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMU:DECYL-BETA-D-MALTOPYRANOSIDE'>DMU</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene><br> |
| - | <b>[[Non-Standard_Residue|NonStd Res:]]</b> <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=DTR:D-TRYPTOPHAN'>DTR</scene>< | + | <tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=DTR:D-TRYPTOPHAN'>DTR</scene></td></tr> |
| - | <b>[[Related_structure|Related:]]</b> [[3wme|3wme]], [[3wmf|3wmf]]< | + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3wme|3wme]], [[3wmf|3wmf]]</td></tr> |
| - | <b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span>< | + | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr> |
| - | <b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3wmg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wmg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wmg RCSB], [http://www.ebi.ac.uk/pdbsum/3wmg PDBsum]</span>< | + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3wmg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wmg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wmg RCSB], [http://www.ebi.ac.uk/pdbsum/3wmg PDBsum]</span></td></tr> |
| + | <table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == 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. | 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. | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | == References == | + | </div>== References == |
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
Revision as of 09:18, 1 May 2014
Crystal structure of an inward-facing eukaryotic ABC multidrug transporter G277V/A278V/A279V mutant in complex with an cyclic peptide inhibitor, aCAP
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