6ob6

From Proteopedia

Human equilibrative nucleoside transporter-1, S-(4-nitrobenzyl)-6-thioinosine bound, merohedrally twinned

PDB ID 6ob6

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Structural highlights

6ob6 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

S29A1_HUMAN Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) and is sodium-independent. It has a higher affinity for adenosine. Inhibited by dipyridamole and dilazep (anticancer chemotherapeutics drugs).

Publication Abstract from PubMed

The human equilibrative nucleoside transporter 1 (hENT1), a member of the SLC29 family, plays crucial roles in adenosine signaling, cellular uptake of nucleoside for DNA and RNA synthesis, and nucleoside-derived anticancer and antiviral drug transport in humans. Because of its central role in adenosine signaling, it is the target of adenosine reuptake inhibitors (AdoRI), several of which are used clinically. Despite its importance in human physiology and pharmacology, the molecular basis of hENT1-mediated adenosine transport and its inhibition by AdoRIs are limited, owing to the absence of structural information on hENT1. Here, we present crystal structures of hENT1 in complex with two chemically distinct AdoRIs: dilazep and S-(4-nitrobenzyl)-6-thioinosine (NBMPR). Combined with mutagenesis study, our structural analyses elucidate two distinct inhibitory mechanisms exhibited on hENT1 and provide insight into adenosine recognition and transport. Our studies provide a platform for improved pharmacological intervention of adenosine and nucleoside analog drug transport by hENT1.

Structures of human ENT1 in complex with adenosine reuptake inhibitors.,Wright NJ, Lee SY Nat Struct Mol Biol. 2019 Jul;26(7):599-606. doi: 10.1038/s41594-019-0245-7. Epub, 2019 Jun 24. PMID:31235912^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wright NJ, Lee SY. Structures of human ENT1 in complex with adenosine reuptake inhibitors. Nat Struct Mol Biol. 2019 Jul;26(7):599-606. doi: 10.1038/s41594-019-0245-7. Epub, 2019 Jun 24. PMID:31235912 doi:http://dx.doi.org/10.1038/s41594-019-0245-7