ArticleThe Journal of biological chemistry2012
Substrate selectivity of YgfU, a uric acid transporter from Escherichia coli.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 48 citations in OpenAlex.
- Reprogramming probiotic for uric acid modular degradation and hyperuricemia treatment by synthetic biology regulation.Microbial cell factories · 2026Article
- Urate metabolism in the gut.Life metabolism · 2026Article
- A reductive uric acid degradation pathway in anaerobic bacteria.Life metabolism · 2025Article
- Designer probiotic-based living drugs for uric acid homeostasis control in hyperuricemic mice and rats.Cell reports. Medicine · 2025Article
- Systematic Engineering for Efficient Uric Acid-Degrading Activity in Probiotic YeastACS synthetic biology · 2025Article
- Article
- Vitamin C transporter SVCT1 serves a physiological role as a urate importer: functional analyses and in vivo investigations.Pflugers Archiv : European journal of physiology · 2023Article
- Rational design of a genome-based insulated system inBioengineering & translational medicine · 2023Article
- EngineeringFrontiers in bioengineering and biotechnology · 2023Article
- [Screening, domestication and identification of intestinal uric acid degrading bacteria in low uric acid population].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2022Article
- Uric acid extrarenal excretion: the gut microbiome as an evident yet understated factor in gout development.Rheumatology international · 2022Review
- Effects of Trace Irrigation at Different Depths on Transcriptome Expression Pattern in Cotton (BioMed research international · 2020Article
- Identification of a Formate-Dependent Uric Acid Degradation Pathway inJournal of bacteriology · 2019Article
- NAT/NCS2-hound: a webserver for the detection and evolutionary classification of prokaryotic and eukaryotic nucleobase-cation symporters of the NAT/NCS2 family.GigaScience · 2018Article
- The solute transport and binding profile of a novel nucleobase cation symporter 2 from the honeybee pathogenFEBS open bio · 2018Article
- Comparative Genomics, Whole-Genome Re-sequencing and Expression Profile Analysis of Nucleobase:Cation Symporter 2 (Frontiers in plant science · 2018Article
- The Aspergillus nidulans proline permease as a model for understanding the factors determining substrate binding and specificity of fungal amino acid transporters.The Journal of biological chemistry · 2015Article
- Functional identification of the hypoxanthine/guanine transporters YjcD and YgfQ and the adenine transporters PurP and YicO of Escherichia coli K-12.The Journal of biological chemistry · 2013Article
- Article
- Insights to the evolution of Nucleobase-Ascorbate Transporters (NAT/NCS2 family) from the Cys-scanning analysis of xanthine permease XanQ.International journal of biochemistry and molecular biology · 2012Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitous nucleobase-ascorbate transporter (NAT/NCS2) family includes more than 2,000 members, but only 15 have been characterized experimentally. Escherichia coli has 10 members, of which the uracil permease UraA and the xanthine permeases XanQ and XanP are functionally known. Of the remaining members, YgfU is closely related in sequence and genomic locus with XanQ. We analyzed YgfU and showed that it is a proton-gradient dependent, low-affinity (K(m) 0.5 mM), and high-capacity transporter for uric acid. It also shows a low capacity for transport of xanthine at 37 °C but not at 25 °C. Based on the set of positions delineated as important from our previous Cys-scanning analysis of permease XanQ, we subjected YgfU to rationally designed site-directed mutagenesis. The results show that the conserved His-37 (TM1), Glu-270 (TM8), Asp-298 (TM9), and Gln-318 and Asn-319 (TM10) are functionally irreplaceable, and Thr-100 (TM3) is essential for the uric acid selectivity because its replacement with Ala allows efficient uptake of xanthine. The key role of these residues is corroborated by the conservation pattern and homology modeling on the recently described x-ray structure of permease UraA. In addition, site-specific replacements at TM8 (S271A, M274D, V282S) impair expression in the membrane, and V320N (TM10) inactivates the permease, whereas R327G (TM10) or S426N (TM14) reduces the affinity for uric acid (4-fold increased K(m)). Our study shows that comprehensive analysis of structure-function relationships in a newly characterized transporter can be accomplished with relatively few site-directed replacements, based on the knowledge available from Cys-scanning mutagenesis of a prototypic homolog.
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