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2.6 OTHER IMPORTANT CATION TRANSPORTERS: SLC19A2, SLC19A3 (THIAMINE TRANSPORTERS), SLC29A4 (MONOAMINE TRANSPORTER) 2.6.1 Introduction

Оглавление

SLC19A2, SLC19A3 and SLC29A4 encode for the transporters THTR‐1, THTR‐2, and PMAT, respectively, and serve as additional important cation transporters while not belonging to the SLC22 family. The main substrate of THTR‐1 and THTR‐2 is thiamine, also known as water‐soluble vitamin B1. Thiamine, a cation at physiological pH, is an essential vitamin, which catalyzes many important reactions involved in cellular metabolism. THTR‐1 and THTR‐2 are high‐affinity, facilitated (energy‐independent) transporters that distribute thiamine and other cationic substrates into the systemic circulation and other tissues in accordance with the substrate’s concentration gradient [3]. SLC19A2 was first cloned in 1999 and encodes for the 497 amino acid THTR‐1 protein with a predicted molecular weight of 55.4 kDa. SLC19A3, cloned a year later, encodes for a 496 amino acid THTR‐2 protein with a predicted molecular weight of 55.6 kDa [53]. The two transporters share 48% sequence identity. Like transporters in the SLC22 family, THTR‐1 and THTR‐2 consist of 12 transmembrane domains and extracellular and intracellular loops [53]. Though crystal structures of a prokaryotic thiamine transporter that binds and transports thiamine are available, neither THTR‐1 nor THTR‐2 have been crystallized [54].

Plasma membrane monoamine transporter (PMAT) is part of the SLC29 family, which is considered to be a major transporter family for nucleosides and nucleoside analogs. Interestingly, PMAT (SLC29A4) was discovered to transport a variety of organic cations and key neurotransmitters in a low‐affinity, high‐capacity manner. Consisting of 530 amino acids, PMAT has a predicted molecular weight of 58 kDa. PMAT does not share significant homology with known neurotransmitter transporters but exhibits minimal homology (~20%) to other members of the SLC29 (ENT) family [4]. There are no x‐ray crystallography or cryo‐electron microscopy structures of human PMAT, but structures exist for human equilibrative nucleoside transporter 1 (hENT1).

Drug Transporters

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