ABCB1 p.Glu325Ala
| Predicted by SNAP2: | A: N (53%), C: D (59%), D: N (66%), F: D (75%), G: N (57%), H: D (63%), I: D (75%), K: N (53%), L: D (80%), M: D (75%), N: N (61%), P: D (85%), Q: N (72%), R: N (66%), S: N (61%), T: N (66%), V: D (71%), W: D (80%), Y: D (71%), |
| 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, |
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[hide] A key structural domain of the Candida albicans Md... Biochem J. 2012 Aug 1;445(3):313-22. Mandal A, Kumar A, Singh A, Lynn AM, Kapoor K, Prasad R
A key structural domain of the Candida albicans Mdr1 protein.
Biochem J. 2012 Aug 1;445(3):313-22., [PMID:22587419]
Abstract [show]
A major multidrug transporter, MDR1 (multidrug resistance 1), a member of the MFS (major facilitator superfamily), invariably contributes to an increased efflux of commonly used azoles and thus corroborates their direct involvement in MDR in Candida albicans. The Mdr1 protein has two transmembrane domains, each comprising six transmembrane helices, interconnected with extracellular loops and ICLs (intracellular loops). The introduction of deletions and insertions through mutagenesis was used to address the role of the largest interdomain ICL3 of the MDR1 protein. Most of the progressive deletants, when overexpressed, eliminated the drug resistance. Notably, restoration of the length of the ICL3 by insertional mutagenesis did not restore the functionality of the protein. Interestingly, most of the insertion and deletion variants of ICL3 became amenable to trypsinization, yielding peptide fragments. The homology model of the Mdr1 protein showed that the molecular surface-charge distribution was perturbed in most of the ICL3 mutant variants. Taken together, these results provide the first evidence that the CCL (central cytoplasmic loop) of the fungal MFS transporter of the DHA1 (drug/proton antiporter) family is critical for the function of MDR. Unlike other homologous proteins, ICL3 has no apparent role in imparting substrate specificity or in the recruitment of the transporter protein.
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No. Sentence Comment
134 The majority of the charged amino acids of ICL3 are functionally critical A close examination of the ICL3 sequence reveals that the positively charged amino acid residues, i.e. K301A, R306A, K307A, K309A, R310A, R312A, R319A, K330A and H334A, are mostly confined to the N-terminal half of the loop, whereas the negatively charged amino acids, i.e. E297A, D318A, E323A, E325A, E327A, E335A, D339A, E346A and E351A, are predominantly clustered towards the C-terminal half (Figure 1 and Supplementary Figure S2C).
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ABCB1 p.Glu325Ala 22587419:134:369
status: NEW