ArticleBiochemistry2012
The importance of being aromatic: π interactions in sodium symporters.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Molecular Mechanisms and Clinical Applications of SGLT2 Inhibitors in Cardiovascular Diseases.Journal of cardiovascular translational research · 2026Review
- The Role of Tryptophan in π Interactions in Proteins: An Experimental Approach.Journal of the American Chemical Society · 2022Article
- The structure of theProceedings of the National Academy of Sciences of the United States of America · 2021Article
- A conserved and buried edge-to-face aromatic interaction in small ubiquitin-like modifier (SUMO) has a role in SUMO stability and function.The Journal of biological chemistry · 2019Article
- Inhibitor binding mode and allosteric regulation of NaNature communications · 2018Article
- Functional Characterization of the Saccharomyces cerevisiae Equilibrative Nucleoside Transporter 1 (ScENT1).Molecules (Basel, Switzerland) · 2018Article
- Iodide Binding in Sodium-Coupled Cotransporters.Journal of chemical information and modeling · 2017Article
- Active site voltage clamp fluorometry of the sodium glucose cotransporter hSGLT1.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Structural and functional significance of water permeation through cotransporters.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- A virtual screen discovers novel, fragment-sized inhibitors of Mycobacterium tuberculosis InhA.Journal of chemical information and modeling · 2015Article
- Structural dynamics of the monoamine transporter homolog LeuT from accelerated conformational sampling and channel analysis.Proteins · 2014Article
- FUN26 (function unknown now 26) protein from saccharomyces cerevisiae is a broad selectivity, high affinity, nucleoside and nucleobase transporter.The Journal of biological chemistry · 2014Article
- Functional identification and characterization of sodium binding sites in Na symporters.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In the LeuT family of sodium solute symporters, 13-17% of the residues in transmembrane domains are aromatic. The unique properties of aromatic amino acids allow them to play specialized roles in proteins, but their function in membrane transporters is underappreciated. Here we analyze the π bonding pattern in the LeuT (5TMIR) family and then describe the role of a triad of aromatic residues in sodium-dependent sugar cotransporters (SGLTs). In SLC5 symporters, three aromatic residues in TM6 (SGLT1 W289, Y290, and W291) are conserved in only those transporting sugars and inositols. We used biophysical analysis of mutants to discover their functional roles, which we have interpreted in terms of CH-π, π-π, and cation-π bonding. We discovered that (1) glucose binding involves CH-π stacking with Y290, (2) π T-stacking interactions between Y290 and W291 and H-bonding between Y290 and N78 (TM1) are essential to form the sodium and sugar binding sites, (3) the Na(+):sugar stoichiometry is determined by these residues, and (4) W289 may be important in stabilizing the structure through H-bonding to TM3. We also find that the WYW triad plays a role in Na(+) coordination at the Na1 site, possibly through cation-π interactions. Surprisingly, this Na(+) is not necessarily coupled to glucose translocation. Our analysis of π interactions in other LeuT proteins suggests that they also contribute to the structure and function in this whole family of transporters.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.