7dl9
From Proteopedia
Crystal structure of nucleoside transporter NupG
Structural highlights
Function[NUPG_ECOLI] Broad-specificity transporter of purine and pyrimidine nucleosides. Driven by a proton motive force. Can transport uridine, adenosine, inosine, guanosine, thymidine and cytidine. Can also transport xanthosine, but with a very low affinity.[1] [2] [3] [4] [5] Publication Abstract from PubMedNucleoside homeostasis, which is mediated by transporters and channels, is essential for all life on Earth. In Escherichia coli, NupG mediates the transport of nucleosides and was deemed to be the prototype of the nucleoside proton symporter (NHS) family as well as the major facilitator superfamily (MFS). To date, the substrate recognition and transport mechanisms of NHS transporters are still elusive. Here, we report two crystal structures of NupG (wild-type and D323A NupG) resolved at 3.0 A. Both structures reveal an identical inward-open conformation. Together with molecular docking and molecular dynamics simulations and in vitro uridine-binding assays, we found that the uridine binding site, which locates in the central cavity between N and C domains of NupG, is constituted by R136, T140, F143, Q225, N228, Q261, E264, Y318, and F322. Moreover, we found that D323 is very important for substrate binding via in vitro uridine-binding assays using D323 mutations, even though it does not have direct contact with uridine. Our structural and biochemical data therefore provide an important framework for the mechanistic understanding of nucleoside transporters of the NHS family. Molecular basis for substrate recognition by the bacterial nucleoside transporter NupG.,Wang C, Xiao Q, Duan H, Li J, Zhang J, Wang Q, Guo L, Hu J, Sun B, Deng D J Biol Chem. 2021 Feb 25:100479. doi: 10.1016/j.jbc.2021.100479. PMID:33640454[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Ecoli | Large Structures | Deng, D | Wang, C | Xiao, Q J | Membrane protein | Mf | Nucleoside | Transport protein | Transporter
