Evidence map›Paper›PMID 19685173›Full record

ArticlePharmaceutical research2009

Mutagenesis and cysteine scanning of transmembrane domain 10 of the human dipeptide transporter.

Liya Xu, Ian S Haworth, Ashutosh A Kulkarni, Michael B Bolger, Daryl L Davies

Open access · greenAbstract readComparative Study
In one paragraph

Article in Pharmaceutical research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.0field-weighted citation impact, top 23% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

13 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
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  5. Metastatic triple-negative breast cancer patient withCold Spring Harbor molecular case studies · 2017
    Article
  6. Review
  7. Review
  8. Article
  9. Structural basis for dynamic mechanism of proton-coupled symport by the peptide transporter POT.Proceedings of the National Academy of Sciences of the United States of America · 2013
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 4 institutions in 1 country.

Liya XuAlcohol and Brain Research Laboratory, Titus Family Department of Clinical Pharmacy and Pharmaceutical Economics & Policy, School of Pharmacy, University of Southern California, Los Angeles, California 90033, USA.
Ian S Haworth
Ashutosh A Kulkarni
Michael B Bolger
Daryl L Davies
Allergan (United States) · USSimulations Plus (United States) · USSouthern California University for Professional Studies · USUniversity of Southern California · US

Funding

Sites /Mechanisms of Ethanol Action in P2X receptorsR01AA013922 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DAVIES, DARYL L · 2004 to 2009
$1.7M
Pressure-Based Pharmacological Alcoholism TreatmentsR21AA013890 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DAVIES, DARYL L · 2003 to 2005
$488k
NIAAA NIH HHS AA013890NIAAA NIH HHS AA013922NIAAA NIH HHS R01 AA013922NIAAA NIH HHS R21 AA013890
6 · The paper itself

Abstract

purposeThe human dipeptide transporter (hPEPT1) facilitates transport of dipeptides and drugs from the intestine into the circulation. The role of transmembrane domain 10 (TMD10) of hPEPT1 in substrate translocation was investigated using cysteine-scanning mutagenesis with 2-Trimethylammonioethyl methanethiosulfonate (MTSET).

methodsEach amino acid in TMD10 was mutated individually to cysteine, and transport of [(3)H]Gly-Sar was evaluated with and without MTSET following transfection of each mutant in HEK293 cells. Similar localization and expression levels of wild type (WT) hPEPT1 and all mutants were confirmed by immunostaining and biotinylation followed by western blot analysis.

resultsE595C- and G594C-hPEPT1 showed negligible Gly-Sar uptake. E595D-hPEPT1 showed similar uptake to WT-hPEPT1, but E595K- and E595R-hPEPT1 did not transport Gly-Sar. Double mutations E595K/R282E and E595R/R282E did not restore uptake. G594A-hPEPT1 showed similar uptake to WT-hPEPT1, but G594V-hPEPT1 eliminated uptake. Y588C-hPEPT1 showed uptake of 20% that of WT-hPEPT1. MTSET modification supported a model of TMD10 with an amphipathic helix from I585 to V600 and increased solvent accessibility from T601 to F605.

conclusionsOur results suggest that G594 and E595 in TMD10 of hPEPT1 have key roles in substrate transport and that Y588 may have an important secondary mechanistic role.

Indexed as

Mutagenesis, Site-DirectedAmino Acid SubstitutionCell LineCell MembraneCysteineDipeptidesExtracellular SpaceGlutamic AcidGlycineHumansPeptide Transporter 1Protein Structure, TertiaryProtein TransportSymportersTyrosineCysteineDipeptidesGlutamic AcidGlycinePeptide Transporter 1SLC15A1 protein, humanSymportersTyrosine

Identifiers

PMID19685173
PMCPMC2861424
OpenAlexW2053319956

What OpenQuestion holds

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Registered trials

None linked

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.