ABCA1 p.Asp1018Glu
| Predicted by SNAP2: | A: D (53%), C: D (59%), E: D (59%), F: D (66%), G: D (71%), H: D (75%), I: D (63%), K: D (71%), L: D (63%), M: D (59%), N: N (61%), P: D (80%), Q: D (59%), R: D (71%), S: D (59%), T: D (59%), V: D (63%), W: D (80%), Y: D (71%), |
| Predicted by PROVEAN: | A: D, C: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Abc1p is a multidrug efflux transporter that tips ... Antimicrob Agents Chemother. 2009 Feb;53(2):354-69. Epub 2008 Nov 17. Lamping E, Ranchod A, Nakamura K, Tyndall JD, Niimi K, Holmes AR, Niimi M, Cannon RD
Abc1p is a multidrug efflux transporter that tips the balance in favor of innate azole resistance in Candida krusei.
Antimicrob Agents Chemother. 2009 Feb;53(2):354-69. Epub 2008 Nov 17., [PMID:19015352]
Abstract [show]
Most Candida krusei strains are innately resistant to fluconazole (FLC) and can cause breakthrough candidemia in immunocompromised individuals receiving long-term prophylactic FLC treatment. Although the azole drug target, Erg11p, of C. krusei has a relatively low affinity for FLC, drug efflux pumps are also believed to be involved in its innate FLC resistance. We describe here the isolation and characterization of Abc1p, a constitutively expressed multidrug efflux pump, and investigate ERG11 and ABC1 expression in C. krusei. Examination of the ERG11 promoter revealed a conserved azole responsive element that has been shown to be necessary for the transcription factor Upc2p mediated upregulation by azoles in related yeast. Extensive cloning and sequencing identified three distinct ERG11 alleles in one of two C. krusei strains. Functional overexpression of ERG11 and ABC1 in Saccharomyces cerevisiae conferred high levels of resistance to azoles and a range of unrelated Abc1p pump substrates, while small molecule inhibitors of Abc1p chemosensitized C. krusei to azole antifungals. Our data show that despite the presence of multiple alleles of ERG11 in some, likely aneuploid, C. krusei strains, it is mainly the low affinity of Erg11p for FLC, together with the constitutive but low level of expression of the multidrug efflux pump Abc1p, that are responsible for the innate FLC resistance of C. krusei.
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No. Sentence Comment
206 Finally, comparing Abc1p with the small part of Abc1p previously isolated (16) revealed three conservative amino acid differences (I990M, D1018E, and V1019L).
X
ABCA1 p.Asp1018Glu 19015352:206:138
status: NEW204 Finally, comparing Abc1p with the small part of Abc1p previously isolated (16) revealed three conservative amino acid differences (I990M, D1018E, and V1019L).
X
ABCA1 p.Asp1018Glu 19015352:204:138
status: NEW