ABCB1 p.Leu439Cys
| Predicted by SNAP2: | A: D (66%), C: D (53%), D: D (91%), E: D (85%), F: D (71%), G: D (85%), H: D (85%), I: D (53%), K: D (85%), M: N (61%), N: D (85%), P: D (91%), Q: D (80%), R: D (85%), S: D (80%), T: D (80%), V: D (59%), W: D (80%), Y: D (80%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Cysteines 431 and 1074 are responsible for inhibit... J Biol Chem. 2001 Jul 20;276(29):26980-7. Epub 2001 May 16. Urbatsch IL, Gimi K, Wilke-Mounts S, Lerner-Marmarosh N, Rousseau ME, Gros P, Senior AE
Cysteines 431 and 1074 are responsible for inhibitory disulfide cross-linking between the two nucleotide-binding sites in human P-glycoprotein.
J Biol Chem. 2001 Jul 20;276(29):26980-7. Epub 2001 May 16., 2001-07-20 [PMID:11356825]
Abstract [show]
Human wild-type and Cys-less P-glycoproteins were expressed in Pichia pastoris and purified in high yield in detergent-soluble form. Both ran on SDS gels as a single 140-kDa band in the presence of reducing agent and showed strong verapamil-stimulated ATPase activity in the presence of added lipid. The wild type showed spontaneous formation of higher molecular mass species in the absence of reducing agent, and its ATPase was activated by dithiothreitol. Oxidation with Cu(2+) generated the same higher molecular mass species, primarily at 200 and approximately 300 kDa, in high yield. Cross-linking was reversed by dithiothreitol and prevented by pretreatment with N-ethylmaleimide. Using proteins containing different combinations of naturally occurring Cys residues, it was demonstrated that an inhibitory intramolecular disulfide bond forms between Cys-431 and Cys-1074 (located in the Walker A sequences of nucleotide-binding sites 1 and 2, respectively), giving rise to the 200-kDa species. In addition, dimeric P-glycoprotein species ( approximately 300 kDa) form by intermolecular disulfide bonding between Cys-431 and Cys-1074. The ready formation of the intramolecular disulfide between Cys-431 and Cys-1074 establishes that the two nucleotide-binding sites of P-glycoprotein are structurally very close and capable of intimate functional interaction, consistent with available information on the catalytic mechanism. Formation of such a disulfide in vivo could, in principle, underlie a regulatory mechanism and might provide a means of intervention to inhibit P-glycoprotein.
Comments [show]
None has been submitted yet.
No. Sentence Comment
301 In a previous report (42), inhibitory disulfide cross-linking was detected between the natural Cys-1074 residue in NBS2 of human Pgp and the engineered mutant residues Cys-427 (mutation G427C) and Cys-439 (mutation L439C) in NBS1.
X
ABCB1 p.Leu439Cys 11356825:301:215
status: NEW299 In a previous report (42), inhibitory disulfide cross-linking was detected between the natural Cys-1074 residue in NBS2 of human Pgp and the engineered mutant residues Cys-427 (mutation G427C) and Cys-439 (mutation L439C) in NBS1.
X
ABCB1 p.Leu439Cys 11356825:299:215
status: NEW