ABCG2 p.Glu446Ala
| Predicted by SNAP2: | A: D (75%), C: D (80%), D: D (63%), F: D (91%), G: D (80%), H: D (80%), I: D (85%), K: D (91%), L: D (91%), M: D (85%), N: D (80%), P: D (91%), Q: D (66%), R: D (91%), S: D (80%), T: D (80%), V: D (75%), W: D (95%), Y: D (91%), |
| Predicted by PROVEAN: | A: D, C: D, D: N, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: N, R: D, S: D, T: D, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Towards understanding the mechanism of action of t... J Mol Graph Model. 2007 Mar;25(6):837-51. Epub 2006 Aug 30. Li YF, Polgar O, Okada M, Esser L, Bates SE, Xia D
Towards understanding the mechanism of action of the multidrug resistance-linked half-ABC transporter ABCG2: a molecular modeling study.
J Mol Graph Model. 2007 Mar;25(6):837-51. Epub 2006 Aug 30., [PMID:17027309]
Abstract [show]
The ATP-binding cassette protein ABCG2 is a member of a broad family of ABC transporters with potential clinical importance as a mediator of multidrug resistance. We carried out a homology and knowledge-based, and mutationally improved molecular modeling study to establish a much needed structural framework for the protein, which could serve as guidance for further genetic, biochemical, and structural analyses. Based on homology with known structures of both full-length and nucleotide-binding domains (NBD) of ABC transporters and structural knowledge of integral membrane proteins, an initial model of ABCG2 was established. Subsequent refinement to conform to the lipophilic index distributions in the transmembrane domain (TMD) and to the results of site-directed mutagenesis experiments led to an improved model. The complete ABCG2 model consists of two identical subunits facing each other in a closed conformation. The dimeric interface in the nucleotide-binding domain (NBD) involves a characteristic nucleotide sandwich and the interface in the TMD consists of the TM helices 1-3 of one subunit and the helices 5 and 6 of the other. The interface between the NBD and the TMD is bridged by the conserved structural motif between TM2 and TM3, the intracellular domain 1 (ICD1), and the terminal beta-strand (S6) of the central beta-sheet in the NBD. The apparent flexibility of the ICD1 may play a role in transmitting conformational changes from the NBD to the TMD or from the TMD to the NBD.
Comments [show]
None has been submitted yet.
No. Sentence Comment
177 Exhibit reduced transport of mitoxantrone, pheophorbide and basal ATPase activity [17] G406A, G410A, G406A/G410A TM1 Fully functional b E446A,D,G,H,K,R,S TM2 Loss of drug resistance [21] R482G,T,M,S, N,D,K,Y TM3 T or G change produces gain of function mutant.
X
ABCG2 p.Glu446Ala 17027309:177:136
status: VERIFIED