ArticleThe EMBO journal2014
Molecular mechanism of ligand recognition by membrane transport protein, Mhp1.
Article in The EMBO journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Identification of a bacterial NCS1 family transporter enabling high-affinity uptake of the antidiabetic drug metformin.Applied and environmental microbiology · 2026Article
- Structural and functional analysis of themBio · 2026Article
- The last two transmembrane helices in the APC-type FurE transporter act as an intramolecular chaperone essential for concentrative ER-exit.Microbial cell (Graz, Austria) · 2024Article
- The Role of NCS1 in Immunotherapy and Prognosis of Human Cancer.Biomedicines · 2023Article
- High-resolution structures with bound MneLife · 2023Article
- Oligomeric state of the aspartate:alanine transporter from Tetragenococcus halophilus.Journal of biochemistry · 2022Article
- Transmembrane helices 5 and 12 control transport dynamics, substrate affinity, and specificity in the elevator-type UapA transporter.Genetics · 2022Article
- Integrated AlphaFold2 and DEER investigation of the conformational dynamics of a pH-dependent APC antiporter.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structure of cytosine transport protein CodB provides insight into nucleobase-cation symporter 1 mechanism.The EMBO journal · 2022Article
- General principles of secondary active transporter function.Biophysics reviews · 2022Review
- Dormant spores sense amino acids through the B subunits of their germination receptors.Nature communications · 2021Article
- Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology.Advances in experimental medicine and biology · 2021Review
- Extracellular loops matter - subcellular location and function of the lysine transporter Lyp1 from Saccharomyces cerevisiae.The FEBS journal · 2020Article
- Sodium-coupled glucose transport, the SLC5 family, and therapeutically relevant inhibitors: from molecular discovery to clinical application.Pflugers Archiv : European journal of physiology · 2020Review
- Mapping of Ion and Substrate Binding Sites in Human Sodium Iodide Symporter (hNIS).Journal of chemical information and modeling · 2020Article
- Inter-species variation in monovalent anion substrate selectivity and inhibitor sensitivity in the sodium iodide symporter (NIS).PloS one · 2020Article
- Locking Two Rigid-body Bundles in an Outward-Facing Conformation: The Ion-coupling Mechanism in a LeuT-fold Transporter.Scientific reports · 2019Article
- Yeast α-arrestin Art2 is the key regulator of ubiquitylation-dependent endocytosis of plasma membrane vitamin B1 transporters.PLoS biology · 2019Article
- Tales of tails in transporters.Open biology · 2019Review
- Screening of candidate substrates and coupling ions of transporters by thermostability shift assays.eLife · 2018Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
The hydantoin transporter Mhp1 is a sodium-coupled secondary active transport protein of the nucleobase-cation-symport family and a member of the widespread 5-helix inverted repeat superfamily of transporters. The structure of Mhp1 was previously solved in three different conformations providing insight into the molecular basis of the alternating access mechanism. Here, we elucidate detailed events of substrate binding, through a combination of crystallography, molecular dynamics, site-directed mutagenesis, biochemical/biophysical assays, and the design and synthesis of novel ligands. We show precisely where 5-substituted hydantoin substrates bind in an extended configuration at the interface of the bundle and hash domains. They are recognised through hydrogen bonds to the hydantoin moiety and the complementarity of the 5-substituent for a hydrophobic pocket in the protein. Furthermore, we describe a novel structure of an intermediate state of the protein with the external thin gate locked open by an inhibitor, 5-(2-naphthylmethyl)-L-hydantoin, which becomes a substrate when leucine 363 is changed to an alanine. We deduce the molecular events that underlie acquisition and transport of a ligand by Mhp1.
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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.