Evidence map›Paper›PMID 42289603›Full record

ArticleActa physiologica (Oxford, England)2026

Phenylalanine Versus Tyrosine (Pos. 367/332 in MCT1/MCT4) in the Substrate Binding Site Defines Affinity and Preferred Directionality of Human Monocarboxylate Transporters 1-4.

Maike Menzel, Ioana-Daniela Dumitru, Josh Peters, Jan-Bernd Hövener, Andrey N Pravdivtsev, Ana-Nicoleta Bondar, Eric Beitz

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In one paragraph

Article in Acta physiologica (Oxford, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

7 authors.

Maike MenzelDepartment of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, Kiel University, Kiel, Germany.
Ioana-Daniela DumitruFaculty of Physics, University of Bucharest, Bucharest, Romania.
Josh PetersSection Biomedical Imaging, Molecular Imaging North Competence Center, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany.
Jan-Bernd HövenerSection Biomedical Imaging, Molecular Imaging North Competence Center, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany.
Andrey N PravdivtsevSection Biomedical Imaging, Molecular Imaging North Competence Center, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany.
Ana-Nicoleta BondarFaculty of Physics, University of Bucharest, Bucharest, Romania.
Eric BeitzDepartment of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, Kiel University, Kiel, Germany.

Funding

Bundesministerium für Bildung und Forschung 03WIR6208AChristian-Albrechts-Universität zu KielDeutsche Forschungsgemeinschaft 469366436Deutsche Forschungsgemeinschaft 527469039Deutsche Forschungsgemeinschaft 555951950Deutsche Forschungsgemeinschaft EXC2167Deutsche Forschungsgemeinschaft FOR5042Deutsche Forschungsgemeinschaft HO-4602/2-2Deutsche Forschungsgemeinschaft HO-4602/3Deutsche Forschungsgemeinschaft TRR287Doctoral School of the Faculty of Physics of the University of BucharestEuropean Commission 101227436European Commission 860592European Regional Development FundJülich Supercomputing Centre, Forschungszentrum JülichKiel University Medical FacultyZukunftsprogramm Wirtschaft of Schleswig-Holstein 122-09-053
6 · The paper itself

Abstract

aimHuman monocarboxylate transporters 1-4, MCT, are key for the lactate/H

methodsHere, we analyzed structural differences in the binding sites of MCT1-4 and determined their impact on the biophysical transport properties and inhibitor binding using radiolabeled transport assays in yeast.

resultsWe found differences in amino acid positions with sidechain hydroxyl groups. While the higher affinity MCT1 and MCT2 carry Phe/Ser-OH (pos. 367/371 in MCT1), the lower affinity MCT3 and MCT4 have Tyr-OH/Gly. Mutation of Phe/Ser-OH in MCT1 to Tyr-OH/Gly markedly decreased the affinity for lactate and pyruvate, while it did not change the affinity for propionate. The maximal transport velocity increased with decreasing affinity, and the preferred transport directionality shifted toward export. Likewise, replacing Met151 by Ala shifted transport bias possibly by eliminating conformation-stabilizing sulfur-aromatic interactions. Moreover, these mutations lowered the activity of the clinical candidate MCT1 inhibitor AZD3965 by three orders of magnitude providing insight into the molecular drug binding mode and explaining the strong preference for MCT1 over MCT4.

conclusionsTogether, subtle changes in the arrangement of sidechains in the MCT binding site determine basic monocarboxylate/H

Indexed as

Monocarboxylic Acid TransportersMuscle ProteinsPhenylalanineSymportersTyrosineBinding SitesBiological TransportHumansMonocarboxylate Transport Protein 1Substrate SpecificityMonocarboxylate Transport Protein 1Monocarboxylic Acid TransportersMuscle ProteinsPhenylalanineSLC16A4 protein, humanSymportersTyrosineaffinitybinding sitedirectionalityhyperpolarizationinhibitorlactatemutationtransport

Identifiers

PMID42289603
PMCPMC13265630

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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.