Equilibrative nucleoside transporters—A review

ABSTRACT

Equilibrative nucleoside transporters (ENTs) are polytopic integral membrane proteins that mediate the transport of nucleosides, nucleobases, and therapeutic analogs. The best-characterized ENTs are the human transporters hENT1 and hENT2. However, non-mammalian eukaryotic ENTs have also been studied (e.g., yeast, parasitic protozoa). ENTs are major pharmaceutical targets responsible for modulating the efficacy of more than 30 approved drugs. However, the molecular mechanisms and chemical determinants of ENT-mediated substrate recognition, binding, inhibition, and transport are poorly understood. This review highlights findings on the characterization of ENTs by surveying studies on genetics, permeant and inhibitor interactions, mutagenesis, and structural models of ENT function.

KEYWORDS:

• Nucleoside transport
• nucleobase transport
• equilibrative nucleoside transporter
• membrane protein

Acknowledgments

We thank Jennifer M. Johnson and Dr. Yuko Tsutsui at the University of Oklahoma Health Sciences Center for helpful comments and suggestions.

Funding sources

Authors of this review would like to acknowledge support from an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103639, Oklahoma Center for the Advancement of Science grant HR11-046 (to F.A.H.), OUHSC College of Medicine Alumni Association seed grant (to F.A.H.), and American Heart Association predoctoral fellowship 13PRE17040024 (to R.C.B-C.).

Notes

The authors declare no competing financial interest.