Genomes and Genes
nucleoside transport proteins
Summary: Proteins involved in the transport of NUCLEOSIDES across cellular membranes.
- Huang Q, Yao S, Ritzel M, Paterson A, Cass C, Young J. Cloning and functional expression of a complementary DNA encoding a mammalian nucleoside transport protein. J Biol Chem. 1994;269:17757-60 pubmed..cNT1 therefore belongs to a potential new gene family and may be involved in the intestinal absorption and renal handling of pyrimidine nucleoside analogs used to treat acquired immunodeficiency syndrome (AIDS). ..
- Pastor Anglada M, Cano Soldado P, Molina Arcas M, Lostao M, Larráyoz I, Martinez Picado J, et al. Cell entry and export of nucleoside analogues. Virus Res. 2005;107:151-64 pubmed..The basic properties of these carrier proteins and their respective role in the transport across the plasma membrane of nucleoside-derived antiviral drugs are reviewed. ..
- Belenky P, Moga T, Brenner C. Saccharomyces cerevisiae YOR071C encodes the high affinity nicotinamide riboside transporter Nrt1. J Biol Chem. 2008;283:8075-9 pubmed publisher..Nrt1-related molecules are conserved in particular fungi, suggesting a similar basis for nicotinamide riboside uptake...
- Loewen S, Ng A, Mohabir N, Baldwin S, Cass C, Young J. Functional characterization of a H+/nucleoside co-transporter (CaCNT) from Candida albicans, a fungal member of the concentrative nucleoside transporter (CNT) family of membrane proteins. Yeast. 2003;20:661-75 pubmedHuman and other mammalian concentrative (Na(+)-linked) nucleoside transport proteins belong to a membrane protein family (CNT, TC 2.A.41) that also includes Escherichia coli H(+)-dependent nucleoside transport protein NupC...
- Casado F, Lostao M, Aymerich I, Larrayoz I, Duflot S, Rodriguez Mulero S, et al. Nucleoside transporters in absorptive epithelia. J Physiol Biochem. 2002;58:207-16 pubmed..Concentrative transporters are found in the apical membrane while equlibrative transporters are located in the basolateral membrane, thus strengthening the hypothesis of a transepithelial flux of nucleosides. ..
- De Koning H, Jarvis S. Uptake of pentamidine in Trypanosoma brucei brucei is mediated by the P2 adenosine transporter and at least one novel, unrelated transporter. Acta Trop. 2001;80:245-50 pubmed..The identity of these transporters was investigated, and their significance for drug uptake and resistance in African trypanosomes is discussed. ..
- Priya T, Philip N, Molho Pessach V, Busa T, Dalal A, Zlotogorski A. H syndrome: novel and recurrent mutations in SLC29A3. Br J Dermatol. 2010;162:1132-4 pubmed publisher..3) In total, 31 patients have been reported in the literature with the clinical phenotype characteristic of this syndrome.(1-7) ..
- Xiao G, Wang J, Tangen T, Giacomini K. A novel proton-dependent nucleoside transporter, CeCNT3, from Caenorhabditis elegans. Mol Pharmacol. 2001;59:339-48 pubmed..The broad nucleoside specificity of CeCNT3 may be explained by this and other residues that restrict purine and pyrimidine nucleoside uptake and that discriminate among pyrimidine nucleosides. ..
- Spiegel R, Cliffe S, Buckley M, Crow Y, Urquhart J, Horovitz Y, et al. Expanding the clinical spectrum of SLC29A3 gene defects. Eur J Med Genet. 2010;53:309-13 pubmed publisher..This report emphasizes the complex genotype phenotype correlation in SLC29A3 disorders and suggests that other factors are relevant to disease manifestations and severity. ..
- Wu W, Sigmond J, Peters G, Borch R. Synthesis and biological activity of a gemcitabine phosphoramidate prodrug. J Med Chem. 2007;50:3743-6 pubmed..The prodrug was more active than gemcitabine against two deoxycytidine kinase-deficient cell lines. The results suggest that the prodrug is a potent growth inhibitor that can bypass dCK deficiency at higher drug concentrations. ..
- Quashie N, Dorin Semblat D, Bray P, Biagini G, Doerig C, Ranford Cartwright L, et al. A comprehensive model of purine uptake by the malaria parasite Plasmodium falciparum: identification of four purine transport activities in intraerythrocytic parasites. Biochem J. 2008;411:287-95 pubmed publisher..We thus propose a model for purine salvage in P. falciparum, based on the highly efficient uptake of hypoxanthine by PfNT1 and a high capacity for purine nucleoside uptake by a lower affinity carrier. ..
- Baldwin S, Yao S, Hyde R, Ng A, Foppolo S, Barnes K, et al. Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. J Biol Chem. 2005;280:15880-7 pubmed..However, it was strongly dependent upon pH, and the optimum pH value of 5.5 probably reflected the location of the transporter in acidic, intracellular compartments. ..
- Gray J, Owen R, Giacomini K. The concentrative nucleoside transporter family, SLC28. Pflugers Arch. 2004;447:728-34 pubmed..Further, this family is involved in the absorption and disposition of many nucleoside analogs. Several CNT single nucleoside polymorphisms (SNPs) have been identified, but have yet to be characterized. ..
- de Koning H, Bridges D, Burchmore R. Purine and pyrimidine transport in pathogenic protozoa: from biology to therapy. FEMS Microbiol Rev. 2005;29:987-1020 pubmed..Recent studies are increasingly addressing the structure and substrate recognition mechanisms of these vital transport proteins. ..
- Xie H, Patching S, Gallagher M, Litherland G, Brough A, Venter H, et al. Purification and properties of the Escherichia coli nucleoside transporter NupG, a paradigm for a major facilitator transporter sub-family. Mol Membr Biol. 2004;21:323-36 pubmed..These findings open the way to elucidating the molecular mechanism of transport in this key family of membrane transporters. ..
- Zhang J, Visser F, King K, Baldwin S, Young J, Cass C. The role of nucleoside transporters in cancer chemotherapy with nucleoside drugs. Cancer Metastasis Rev. 2007;26:85-110 pubmed
- Govindarajan R, Leung G, Zhou M, Tse C, Wang J, Unadkat J. Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by human equilibrative nucleoside transporter-3. Am J Physiol Gastrointest Liver Physiol. 2009;296:G910-22 pubmed publisher..In addition, our finding that hENT3 is a mitochondrial transporter is consistent with the recent finding that mutations in the hENT3 gene cause an autosomal recessive disorder in humans called the H syndrome. ..
- Mangravite L, Badagnani I, Giacomini K. Nucleoside transporters in the disposition and targeting of nucleoside analogs in the kidney. Eur J Pharmacol. 2003;479:269-81 pubmed..This review examines the role that these transporters play in renal disposition of nucleosides and nucleoside analogs in both systemic and kidney-specific therapies. ..
- Cliffe S, Kramer J, Hussain K, Robben J, de Jong E, de Brouwer A, et al. SLC29A3 gene is mutated in pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome and interacts with the insulin signaling pathway. Hum Mol Genet. 2009;18:2257-65 pubmed publisher..These data suggest that further investigation of the role of SLC29A3 in glucose metabolism is a priority for diabetes research. ..
- Huber Ruano I, Pastor Anglada M. Transport of nucleoside analogs across the plasma membrane: a clue to understanding drug-induced cytotoxicity. Curr Drug Metab. 2009;10:347-58 pubmed
- Wallace L, Candlish D, de Koning H. Different substrate recognition motifs of human and trypanosome nucleobase transporters. Selective uptake of purine antimetabolites. J Biol Chem. 2002;277:26149-56 pubmed..The potential for selective uptake of antimetabolites by the parasite transporter was demonstrated. ..
- Morgan N, Morris M, Cangul H, Gleeson D, Straatman Iwanowska A, Davies N, et al. Mutations in SLC29A3, encoding an equilibrative nucleoside transporter ENT3, cause a familial histiocytosis syndrome (Faisalabad histiocytosis) and familial Rosai-Dorfman disease. PLoS Genet. 2010;6:e1000833 pubmed publisher..Our findings suggest that a variety of clinical diagnoses (H and PHID syndromes, FHC, and familial RDD) can be included in a new diagnostic category of SLC29A3 spectrum disorder. ..
- M ser P, S tterlin C, Kralli A, Kaminsky R. A nucleoside transporter from Trypanosoma brucei involved in drug resistance. Science. 1999;285:242-4 pubmed..Drug-resistant trypanosomes harbor a defective TbAT1 variant. The molecular identification of the entry route of trypanocides opens the way to approaches for diagnosis and treatment of drug-resistant sleeping sickness...
- Parkinson F, Damaraju V, Graham K, Yao S, Baldwin S, Cass C, et al. Molecular biology of nucleoside transporters and their distributions and functions in the brain. Curr Top Med Chem. 2011;11:948-72 pubmed
- Plagemann P, Woffendin C. Species differences in sensitivity of nucleoside transport in erythrocytes and cultured cells to inhibition by nitrobenzylthioinosine, dipyridamole, dilazep and lidoflazine. Biochim Biophys Acta. 1988;969:1-8 pubmed..In addition HeLa cells and clones thereof expressed uridine transporters (about 50% each) with difference of about 1000-fold in sensitivity to inhibition by dilazep (IC50 approx. 5 nM and 5 microM, respectively). ..
- King A, Ackley M, Cass C, Young J, Baldwin S. Nucleoside transporters: from scavengers to novel therapeutic targets. Trends Pharmacol Sci. 2006;27:416-25 pubmed..The therapeutic use of nucleoside analogue drugs and nucleoside transporter inhibitors in viral, neoplastic, cardiovascular and infectious disease is also described. ..
- Al Salabi M, Wallace L, Lüscher A, Maser P, Candlish D, Rodenko B, et al. Molecular interactions underlying the unusually high adenosine affinity of a novel Trypanosoma brucei nucleoside transporter. Mol Pharmacol. 2007;71:921-9 pubmed..We show that both TbNT9/AT-D and NT10/AT-B transport a range of potentially therapeutic nucleoside analogs. ..
- Soler C, Garcia Manteiga J, Valdes R, Xaus J, Comalada M, Casado F, et al. Macrophages require different nucleoside transport systems for proliferation and activation. FASEB J. 2001;15:1979-88 pubmed..This report also shows that the nucleoside transporters are critical for macrophage proliferation and activation. ..
- Pastor Anglada M, Molina Arcas M, Casado F, Bellosillo B, Colomer D, Gil J. Nucleoside transporters in chronic lymphocytic leukaemia. Leukemia. 2004;18:385-93 pubmed..As long as nucleoside transporter expression in leukaemia cells is not constitutive, the possibility of regulating nucleoside transporter function by pharmacological means may also contribute to improve therapy. ..
- Yong T, Chen S, Xie Y, Chen D, Su J, Shuai O, et al. Hypouricemic Effects of Armillaria mellea on Hyperuricemic Mice Regulated through OAT1 and CNT2. Am J Chin Med. 2018;46:585-599 pubmed publisher..From the analysis, we concluded that hydrogen bond, Pi-Pi and Pi-sigma interactions might play important roles for their orientations and locations in XOD inhibition. ..
- Markovic I, Segal M, Djuricic B, Redzic Z. Kinetics of nucleoside uptake by the basolateral side of the sheep choroid plexus epithelium perfused in situ. Exp Physiol. 2008;93:325-33 pubmed..Considering the estimated K(m,app) values, it appears that under normal conditions inosine is the more important nucleoside substrate for uptake by the basolateral membrane of the choroid plexus epithelium than other nucleosides. ..
- Farr S, Chess Williams R, McDermott C. Gemcitabine: Selective cytotoxicity, induction of inflammation and effects on urothelial function. Toxicol Appl Pharmacol. 2017;316:1-9 pubmed publisher..The selectivity of gemcitabine for malignant urothelial cells may account for the less frequent adverse urological effects with comparison to other commonly used chemotherapeutic agents. ..
- Ferrandina G, Mey V, Nannizzi S, Ricciardi S, Petrillo M, Ferlini C, et al. Expression of nucleoside transporters, deoxycitidine kinase, ribonucleotide reductase regulatory subunits, and gemcitabine catabolic enzymes in primary ovarian cancer. Cancer Chemother Pharmacol. 2010;65:679-86 pubmed publisher..The assessment of the expression levels of RRM2 as marker of clinical outcome deserves further investigation in a larger series of ovarian cancer patients. ..
- Paes de Carvalho R, Dias B, Martins R, Pereira M, Portugal C, Lanfredi C. Activation of glutamate receptors promotes a calcium-dependent and transporter-mediated release of purines in cultured avian retinal cells: possible involvement of calcium/calmodulin-dependent protein kinase II. Neurochem Int. 2005;46:441-51 pubmed..The regulation of adenosine release by glutamate receptors and CAMK II could have important consequences in the presynaptic control of glutamate release. ..
- Perri D, Ito S, Rowsell V, Shear N. The kidney--the body's playground for drugs: an overview of renal drug handling with selected clinical correlates. Can J Clin Pharmacol. 2003;10:17-23 pubmed..At the patient level, this may lead to novel approaches to alter in vivo pharmacokinetics and improve drug safety through a greater understanding of toxic substrate clearance and drug interactions. ..
- Yabushita Y, Mori R, Taniguchi K, Matsuyama R, Kumamoto T, Sakamaki K, et al. Combined Analyses of hENT1, TS, and DPD Predict Outcomes of Borderline-resectable Pancreatic Cancer. Anticancer Res. 2017;37:2465-2476 pubmed..002). Combined expression analyses of hENT1, TS, and DPD may predict long-term outcomes in patients with BRPC after NACRT. ..
- Qi H, Lu J, Li J, Wang M, Xu Y, Wang Y, et al. Enhanced Antitumor Activity of Monophosphate Ester Prodrugs of Gemcitabine: InÂ Vitro and InÂ Vivo Evaluation. J Pharm Sci. 2016;105:2966-2973 pubmed publisher..Taken together, compound-3 has the potential for further development as an orally active antitumor agent. ..
- Snoeck E, Jacqmin P, Van Peer A, Danhof M. A combined specific target site binding and pharmacokinetic model to explore the non-linear disposition of draflazine. J Pharmacokinet Biopharm. 1999;27:257-81 pubmed..The recovery of draflazine was also dose dependent and increased with increasing doses. Finally, the total CL and apparent Vd of the first dose were greater than those of the second dose of draflazine. ..
- Bohm M, Weinhold C, Schwinger R, Müller Ehmsen J, Bohm D, Reichenspurner H, et al. Studies of the nucleoside transporter inhibitor, draflazine, in the human myocardium. Br J Pharmacol. 1994;112:137-42 pubmed..6. Draflazine could be a useful agent for cardio preservation because it does not produce cardio depressant effects. Thus, it may be possible to perfuse explanted hearts directly with this agent without the hazard of cardiodepression. ..
- El Messaoudi S, Russel F, Colbers A, Bandell C, van den Broek P, Burger D, et al. The effect of dipyridamole on the pharmacokinetics of metformin: a randomized crossover study in healthy volunteers. Eur J Clin Pharmacol. 2016;72:725-30 pubmed publisher..This observation is reassuring for patients who are treated with this combination of drugs. ..
- Gourdeau H, Clarke M, Ouellet F, Mowles D, Selner M, Richard A, et al. Mechanisms of uptake and resistance to troxacitabine, a novel deoxycytidine nucleoside analogue, in human leukemic and solid tumor cell lines. Cancer Res. 2001;61:7217-24 pubmed
- Morita K, Saida M, Morioka N, Kitayama T, Akagawa Y, Dohi T. Cyclic ADP-ribose mediates formyl methionyl leucyl phenylalanine (fMLP)-induced intracellular Ca(2+) rise and migration of human neutrophils. J Pharmacol Sci. 2008;106:492-504 pubmed..This process may be involved in fMLP-induced intracellular Ca(2+) signaling and migration in human neutrophils. ..
- Flanagan S, Meckling K. Nucleoside transporter expression and activity is regulated during granulocytic differentiation of NB4 cells in response to all-trans-retinoic acid. Leuk Res. 2007;31:955-68 pubmed
- Huang H, Wang J, Zhang J, Luo Z, Li D, Qiu X, et al. Nitrobenzylthioinosine mimics adenosine to attenuate the epileptiform discharge of hippocampal neurons from epileptic rats. Oncotarget. 2017;8:35573-35582 pubmed publisher..At the same time, NBTI mimics adenosine to attenuate the epileptiform discharge through adenosine A1 receptor, which might provide a novel therapeutic approach toward the control of epilepsy. ..
- Lanteri C, Stewart M, Brock J, Alibu V, Meshnick S, Tidwell R, et al. Roles for the Trypanosoma brucei P2 transporter in DB75 uptake and resistance. Mol Pharmacol. 2006;70:1585-92 pubmed
- Otsuguro K, Tomonari Y, Otsuka S, Yamaguchi S, Kon Y, Ito S. An adenosine kinase inhibitor, ABT-702, inhibits spinal nociceptive transmission by adenosine release via equilibrative nucleoside transporters in rat. Neuropharmacology. 2015;97:160-70 pubmed publisher..This feature is expected to lead to good analgesic effects, but, caution may be required for the use of AK inhibitors in the case of ADA dysfunction or a combination with ENT inhibitors. ..
- Möhlmann T, Bernard C, Hach S, Ekkehard Neuhaus H. Nucleoside transport and associated metabolism. Plant Biol (Stuttg). 2010;12 Suppl 1:26-34 pubmed publisher..Furthermore, extracellular nucleotide metabolism has become an immensely interesting research topic. In addition, selected aspects of nucleoside transport in yeast, protists and humans are discussed. ..
- Emes R, Yang Z. Duplicated paralogous genes subject to positive selection in the genome of Trypanosoma brucei. PLoS ONE. 2008;3:e2295 pubmed publisher..We discuss how adaptive evolution of these genes may highlight lineage specific processes essential for parasite survival. We also discuss the implications of adaptive evolution of these targets for parasite biology and control. ..
- Domingo P, Torres Torronteras J, Pomar V, Giralt M, Domingo J, Gutierrez M, et al. Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lipodystrophy syndrome. PLoS ONE. 2010;5:e13896 pubmed publisher..Antiretroviral therapy was not associated with plasma uridine concentrations, but pure lipoatrophic HALS was associated with significantly lower plasma uridine concentrations. ..
- Bone D, Robillard K, Stolk M, Hammond J. Differential regulation of mouse equilibrative nucleoside transporter 1 (mENT1) splice variants by protein kinase CK2. Mol Membr Biol. 2007;24:294-303 pubmed..In conclusion, inhibition of CK2 activity, or deletion of Ser(254) from mENT1, enhances transporter affinity for the inhibitor, NBMPR, and reduces the number of ENT1 proteins functioning at the level of the plasma membrane. ..
- Szkotak A, Ng A, Man S, Baldwin S, Cass C, Young J, et al. Coupling of CFTR-mediated anion secretion to nucleoside transporters and adenosine homeostasis in Calu-3 cells. J Membr Biol. 2003;192:169-79 pubmed
- Liu W, Boitz J, Galazka J, Arendt C, Carter N, Ullman B. Functional characterization of nucleoside transporter gene replacements in Leishmania donovani. Mol Biochem Parasitol. 2006;150:300-7 pubmed
- Aymerich I, Duflot S, Fernandez Veledo S, Guillen Gomez E, Huber Ruano I, Casado F, et al. The concentrative nucleoside transporter family (SLC28): new roles beyond salvage?. Biochem Soc Trans. 2005;33:216-9 pubmed..Animal and cell models genetically modified to alter nucleoside transporter expression levels may help to elucidate the particular roles of CNT proteins in cell physiology. ..
- Short J, Ledent C, Borrelli E, Drago J, Lawrence A. Genetic interdependence of adenosine and dopamine receptors: evidence from receptor knockout mice. Neuroscience. 2006;139:661-70 pubmed..These data are consistent with the existence of functional interactions between dopaminergic and purinergic systems in these reward and motor-related brain regions. ..
- Koczor C, Torres R, Lewis W. The role of transporters in the toxicity of nucleoside and nucleotide analogs. Expert Opin Drug Metab Toxicol. 2012;8:665-76 pubmed publisher..However, additional understanding of nucleoside transporter kinetics, tissue expression and genetic polymorphisms is required to design better molecules and better therapies. ..
- Godfrey L, Morselli A, Bennion P, Clarke G, Hourani S, Kitchen I. An investigation of binding sites for paracetamol in the mouse brain and spinal cord. Eur J Pharmacol. 2005;508:99-106 pubmed..Although paracetamol did bind specifically to the murine brain and spinal cord, the binding was not region-specific, suggesting binding is not related to any particular neurotransmitter system. ..
- Ogbunude P, Baer H. Competition of nucleoside transport inhibitors with binding of 6-[(4-nitrobenzyl)-mercapto]purine ribonucleoside to intact erythrocytes and ghost membranes from different species. Biochem Pharmacol. 1990;39:1199-204 pubmed
- Governo R, Deuchars J, Baldwin S, King A. Localization of the NBMPR-sensitive equilibrative nucleoside transporter, ENT1, in the rat dorsal root ganglion and lumbar spinal cord. Brain Res. 2005;1059:129-38 pubmed..The functional significance of ENT1 expression with regard to the homeostatic regulation of adenosine at synapses remains to be established. ..
- Abd Elfattah A, Ding M, Jessen M, Wechsler A. On-pump inhibition of es-ENT1 nucleoside transporter and adenosine deaminase during aortic crossclamping entraps intracellular adenosine and protects against reperfusion injury: role of adenosine A1 receptor. J Thorac Cardiovasc Surg. 2012;144:243-9 pubmed publisher
- Yao S, Ng A, Muzyka W, Griffiths M, Cass C, Baldwin S, et al. Molecular cloning and functional characterization of nitrobenzylthioinosine (NBMPR)-sensitive (es) and NBMPR-insensitive (ei) equilibrative nucleoside transporter proteins (rENT1 and rENT2) from rat tissues. J Biol Chem. 1997;272:28423-30 pubmed..These observations demonstrate that es and ei nucleoside transport activities are mediated by separate, but homologous, proteins and establish a function for the HNP36 gene product. ..
- De Koning H, Watson C, Sutcliffe L, Jarvis S. Differential regulation of nucleoside and nucleobase transporters in Crithidia fasciculata and Trypanosoma brucei brucei. Mol Biochem Parasitol. 2000;106:93-107 pubmed..These results show that regulation of the capacity of the purine transporters is common in different protozoa, and that, in T. b. brucei, various purine transporters are under differential control...
- Petrovic M, Dekanski D, Isakovic A, Scepanovic L, Mitrovic D. Mechanism of 3-deazaguanine transport in the rat heart. Acta Physiol Hung. 2006;93:293-301 pubmed
- Boyer C, Karjian P, Wahl G, Pegram M, Neuteboom S. Nucleoside transport inhibitors, dipyridamole and p-nitrobenzylthioinosine, selectively potentiate the antitumor activity of NB1011. Anticancer Drugs. 2002;13:29-36 pubmed..We demonstrate that nucleoside transport inhibitors, dipyridamole and NBMPR, show promise for clinically efficacious combination with NB1011. ..
- Stewart M, Boussard C, Brun R, Gilbert I, Barrett M. Interaction of monobenzamidine-linked trypanocides with the Trypanosoma brucei P2 aminopurine transporter. Antimicrob Agents Chemother. 2005;49:5169-71 pubmed..Trypanocidal activity was evident, but compounds were equally toxic against trypanosomes lacking the P2 transporter, which indicates additional uptake routes for monobenzamidine-derived compounds. ..
- Eckle T, Grenz A, Kohler D, Redel A, Falk M, Rolauffs B, et al. Systematic evaluation of a novel model for cardiac ischemic preconditioning in mice. Am J Physiol Heart Circ Physiol. 2006;291:H2533-40 pubmed..Further studies on cardiac IP using transgenic mice may consider this technique. ..
- Li G, Liu K, Baldwin S, Wang D. Equilibrative nucleoside transporters of Arabidopsis thaliana. cDNA cloning, expression pattern, and analysis of transport activities. J Biol Chem. 2003;278:35732-42 pubmed..We conclude that AtENT3 represents the first ei type ENT characterized from higher plants. The potential functions of ENTs in the biology of A. thaliana are discussed. ..
- Kong W, Wang J. Hypoxanthine transport in human glioblastoma cells and effect on cell susceptibility to methotrexate. Pharm Res. 2003;20:1804-11 pubmed..At physiologic concentrations, hypoxanthine protects glioblastoma cells from the cytotoxicity of methotrexate. ..
- Arastu Kapur S, Arendt C, Purnat T, Carter N, Ullman B. Second-site suppression of a nonfunctional mutation within the Leishmania donovani inosine-guanosine transporter. J Biol Chem. 2005;280:2213-9 pubmed..The model indicates that Asn(175) and Asp(389) lie in close proximity and that the second-site suppressor mutations cluster to one region of the transporter. ..