<table><tr><td colspan='2'>[[6gdi]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GDI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GDI FirstGlance]. <br>
<table><tr><td colspan='2'>[[6gdi]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GDI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GDI FirstGlance]. <br>
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[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Lk3 transgenic mice]]
Revision as of 21:30, 6 March 2020
Structure of P-glycoprotein(ABCB1) in the post-hydrolytic state
6gdi is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[MDR1A_MOUSE] Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.[1]
Publication Abstract from PubMed
BACKGROUND: P-glycoprotein (ABCB1) is an ATP-binding cassette transporter that plays an important role in the clearance of drugs and xenobiotics and is associated with multi-drug resistance in cancer. Although several P-glycoprotein structures are available, these are either at low resolution, or represent mutated and/or quiescent states of the protein. RESULTS: In the post-hydrolytic state the structure of the wild-type protein has been resolved at about 8 A resolution. The cytosolic nucleotide-binding domains (NBDs) are separated but ADP remains bound, especially at the first NBD. Gaps in the transmembrane domains (TMDs) that connect to an inner hydrophilic cavity are filled by density emerging from the annular detergent micelle. The NBD-TMD linker is partly resolved, being located between the NBDs and close to the Signature regions involved in cooperative NBD dimerization. This, and the gap-filling detergent suggest steric impediment to NBD dimerization in the post-hydrolytic state. Two central regions of density lie in two predicted drug-binding sites, implying that the protein may adventitiously bind hydrophobic substances even in the post-hydrolytic state. The previously unresolved N-terminal extension was observed, and the data suggests these 30 residues interact with the headgroup region of the lipid bilayer. CONCLUSION: The structural data imply that (i) a low basal ATPase activity is ensured by steric blockers of NBD dimerization and (ii) allocrite access to the central cavity may be structurally linked to NBD dimerization, giving insights into the mechanism of drug-stimulation of P-glycoprotein activity.
Novel features in the structure of P-glycoprotein (ABCB1) in the post-hydrolytic state as determined at 7.9 A resolution.,Thonghin N, Collins RF, Barbieri A, Shafi T, Siebert A, Ford RC BMC Struct Biol. 2018 Dec 13;18(1):17. doi: 10.1186/s12900-018-0098-z. PMID:30545335[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
↑ Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, Chang G. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science. 2009 Mar 27;323(5922):1718-22. PMID:19325113 doi:323/5922/1718
↑ Thonghin N, Collins RF, Barbieri A, Shafi T, Siebert A, Ford RC. Novel features in the structure of P-glycoprotein (ABCB1) in the post-hydrolytic state as determined at 7.9 A resolution. BMC Struct Biol. 2018 Dec 13;18(1):17. doi: 10.1186/s12900-018-0098-z. PMID:30545335 doi:http://dx.doi.org/10.1186/s12900-018-0098-z
