Rational Mutational Analysis of a Multidrug Mfs Transporter Camdr1P of Candida Albicans by Employing a Membrane Environment Based Computational Approach.

References: 1. Prasad R, Kapoor K (2005) Multidrug resistance in yeast Candida. Int Rev Cytol 242: 215–248. 2. Gaur M, Choudhury D, Prasad R (2005) Complete inventory of ABC proteins in human pathogenic yeast, Candida albicans. J Mol Microbiol Biotechnol 9: 3–15. 3. Gaur M, Puri N, Manoharlal R, Rai V, Mukhopadhayay G, et al. (2008) MFS transportome of the human pathogenic yeast Candida albicans. BMC Genomics 9: 579. 4. Smriti, Krishnamurthy S, Dixit BL, Gupta CM, Milewski S, et al. (2002) ABC transporters Cdr1p, Cdr2p and Cdr3p of a human pathogen Candida albicans are general phospholipid translocators. Yeast 19: 303–318. 5. De RE, Arrigo P, Bellinzoni M, Silva PA, Martin C, et al. (2002) The multidrug transporters belonging to major facilitator superfamily in Mycobacterium tuberculosis. Mol Med 8: 714–724. 6. Ginn SL, Brown MH, Skurray RA (2000) The TetA(K) tetracycline/H(+) antiporter from Staphylococcus aureus: mutagenesis and functional analysis of motif C. J Bacteriol 182: 1492–1498. 7. Paulsen IT, Brown MH, Skurray RA (1996) Proton-dependent multidrug efflux systems. Microbiol Rev 60: 575–608. 8. Law CJ, Maloney PC, Wang DN (2008) Ins and outs of major facilitator superfamily antiporters. Annu Rev Microbiol 62: 289–305. PLoS Computational Biology | www.ploscompbiol.org 10 December 2009 | Volume 5 | Issue 12 | e1000624 Mutational Analysis of a Multidrug MFS Transporter 9. Abramson J, Smirnova I, Kasho V, Verner G, Kaback HR, et al. (2003) Structure and mechanism of the lactose permease of Escherichia coli. Science 301: 610–615. 10. Huang Y, Lemieux MJ, Song J, Auer M, Wang DN (2003) Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli. Science 301: 616–620. 11. Yin Y, He X, Szewczyk P, Nguyen T, Chang G (2006) Structure of the multidrug transporter EmrD from Escherichia coli. Science 312: 741–744. 12. Yang Q, Wang X, Ye L, Mentrikoski M, Mohammadi E, et al. (2005) Experimental tests of a homology model for OxlT, the oxalate transporter of Oxalobacter formigenes. Proc Natl Acad Sci U S A 102: 8513–8518. 13. Sa-Correia I, dos Santos SC, Teixeira MC, Cabrito TR, Mira NP (2009) Drug:H+ antiporters in chemical stress response in yeast. Trends Microbiol 17: 22–31. 14. Pao SS, Paulsen IT, Saier MH Jr (1998) Major Facilitator Superfamily. Microbiol Mol Biol Rev 62: 1–34. 15. Egner R, Bauer BE, Kuchler K (2000) The transmembrane domain 10 of the yeast Pdr5p ABC antifungal efflux pump determines both substrate specificity and inhibitor susceptibility. Mol Microbiol 35: 1255–1263. 16. Shukla S, Robey RW, Bates SE, Ambudkar SV (2006) The calcium channel blockers, 1,4-dihydropyridines, are substrates of the multidrug resistance-linked ABC drug transporter, ABCG2. Biochemistry 45: 8940–8951. 17. Tutulan-Cunita AC, Mikoshi M, Mizunuma M, Hirata D, Miyakawa T (2005) Mutational analysis of the yeast multidrug resistance ABC transporter Pdr5p with altered drug specificity. Genes Cells 10: 409–420. 18. Ernst R, Kueppers P, Klein CM, Schwarzmueller T, Kuchler K, et al. (2008) A mutation of the H-loop selectively affects rhodamine transport by the yeast multidrug ABC transporter Pdr5. Proc Natl Acad Sci U S A 105: 5069–5074. 19. Saini P, Prasad T, Gaur NA, Shukla S, Jha S, et al. (2005) Alanine scanning of transmembrane helix 11 of Cdr1p ABC antifungal efflux pump of Candida albicans: identification of amino acid residues critical for drug efflux. J Antimicrob Chemother 56: 77–86. 20. Puri N, Gaur M, Sharma M, Shukla S, Ambudkar SV, et al. (2009) The amino acid residues of transmembrane helix 5 of multidrug resistance protein CaCdr1p of Candida albicans are involved in substrate specificity and drug transport. Biochim Biophys Acta 1788: 1752–1761. 21. Krogh A, Larsson B, von HG, Sonnhammer EL (2001) Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 305: 567–580. 22. Ng PC, Henikoff JG, Henikoff S (2000) PHAT: a transmembrane-specific substitution matrix. Bioinformatics 16: 760–766. 23. Valdar WS (2002) Scoring residue conservation. Proteins 48: 227–241. 24. Cover T, Thomas J (2009) Elements of Information Theory. 25. Shannon CE (1997) The mathematical theory of communication. 1963. MD Comput 14: 306–317. 26. Wang K, Samudrala R (2006) Incorporating background frequency improves entropy-based residue conservation measures. BMC Bioinformatics 7: 385. 27. Hannenhalli SS, Russell RB (2000) Analysis and prediction of functional subtypes from protein sequence alignments. J Mol Biol 303: 61–76. 28. Srivastava PK, Desai DK, Nandi S, Lynn AM (2007) HMM-ModE improved classification using profile hidden Markov models by optimising the discrimination threshold and modifying emission probabilities with negative training sequences. BMC Bioinformatics 8: 104. 29. Reva B, Antipin Y, Sander C (2007) Determinants of protein function revealed by combinatorial entropy optimization. Genome Biol 8: R232. 30. Li L, Shakhnovich EI, Mirny LA (2003) Amino acids determining enzymesubstrate specificity in prokaryotic and eukaryotic protein kinases. Proc Natl Acad Sci U S A 100: 4463–4468. 31. Fischer JD, Mayer CE, Soding J (2008) Prediction of protein functional residues from sequence by probability density estimation. Bioinformatics 24: 613–620. 32. Capra JA, Singh M (2008) Characterization and prediction of residues determining protein functional specificity. Bioinformatics 24: 1473–1480. 33. Decottignies A, Grant AM, Nichols JW, De Wet H, McIntosh DB, et al. (1998) ATPase and multidrug transport activities of the overexpressed yeast ABC protein Yor1p. J Biol Chem 273: 12612–12622. 34. Nakamura K, Niimi M, Niimi K, Holmes AR, Yates JE, et al. (2001) Functional expression of Candida albicans drug efflux pump Cdr1p in a Saccharomyces cerevisiae strain deficient in membrane transporters. Antimicrob Agents Chemother 45: 3366–3374. 35. Pasrija R, Banerjee D, Prasad R (2007) Structure and function analysis of CaMdr1p, a major facilitator superfamily antifungal efflux transporter protein of Candida albicans: identification of amino acid residues critical for drug/H+ transport. Eukaryot Cell 6: 443–453. 36. Pirovano W, Feenstra KA, Heringa J (2008) PRALINETM: a strategy for improved multiple alignment of transmembrane proteins. Bioinformatics 24: 492–497. 37. Ditty JL, Harwood CS (1999) Conserved cytoplasmic loops are important for both the transport and chemotaxis functions of PcaK, a protein from Pseudomonas putida with 12 membrane-spanning regions. J Bacteriol 181: 5068–5074. 38. Guan L, Kaback HR (2006) Lessons from lactose permease. Annu Rev Biophys Biomol Struct 35: 67–91. 39. Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32: 1792–1797. 40. Henikoff S, Henikoff JG (1992) Amino acid substitution matrices from protein blocks. Proc Natl Acad Sci U S A 89: 10915–10919. 41. Chandrasekaran A, Ojeda AM, Kolmakova NG, Parsons SM (2006) Mutational and bioinformatics analysis of proline- and glycine-rich motifs in vesicular acetylcholine transporter. J Neurochem 98: 1551–1559. 42. Martin LC, Gloor GB, Dunn SD, Wahl LM (2005) Using information theory to search for co-evolving residues in proteins. Bioinformatics 21: 4116–4124. 43. Koike K, Oleschuk CJ, Haimeur A, Olsen SL, Deeley RG, et al. (2002) Multiple membrane-associated tryptophan residues contribute to the transport activity and substrate specificity of the human multidrug resistance protein, MRP1. J Biol Chem 277: 49495–49503. 44. Schiffer M, Chang CH, Stevens FJ (1992) The functions of tryptophan residues in membrane proteins. Protein Eng 5: 213–214. 45. Chen CP, Kernytsky A, Rost B (2002) Transmembrane helix predictions revisited. Protein Sci 11: 2774–2791. 46. Shukla S, Saini P, Smriti, Jha S, Ambudkar SV, et al. (2003) Functional characterization of Candida albicans ABC transporter Cdr1p. Eukaryot Cell 2: 1361–1375. 47. Sali A, Blundell TL (1993) Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234: 779–815. 48. Barton GJ (1993) ALSCRIPT: a tool to format multiple sequence alignments. Protein Eng 6: 37–40. 49. Livingstone CD, Barton GJ (1993) Protein sequence alignments: a strategy for the hierarchical analysis of residue conservation. Comput Appl Biosci 9: 745–756. 50. Sigal N, Molshanski-Mor S, Bibi E (2006) No single irreplaceable acidic residues in the Escherichia coli secondary multidrug transporter MdfA. J Bacteriol 188: 5635–5639. PLoS Computational Biology | www.ploscompbiol.org 11 December 2009 | Volume 5 | Issue 12 | e1000624