Evidence map›Paper›PMID 17009102›Full record

ArticlePharmaceutical research2007

A charge pair interaction between Arg282 in transmembrane segment 7 and Asp341 in transmembrane segment 8 of hPepT1.

Ashutosh A Kulkarni, Daryl L Davies, Jennifer S Links, Leena N Patel, Vincent H L Lee, Ian S Haworth

Abstract read
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In one paragraph

Article in Pharmaceutical research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

12 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
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  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review. The mammalian proton-coupled peptide cotransporter PepT1: sitting on the transporter-channel fence?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2009
    Review
  11. Article
  12. Article
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

6 authors at 1 institution in 1 country.

Ashutosh A KulkarniDepartment of Pharmaceutical Sciences, University of Southern California, 1985 Zonal Avenue, Los Angeles, California 90089-9121, USA.
Daryl L Davies
Jennifer S Links
Leena N Patel
Vincent H L Lee
Ian S Haworth
University of Southern California · US

Funding

PEPT1: STRUCTURE-FUNCTION, SORTING AND MODULATIONR01GM059297 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HAWORTH, IAN S · 2000 to 2003
$1.3M
Pressure-Based Pharmacological Alcoholism TreatmentsR21AA013890 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DAVIES, DARYL L · 2003 to 2005
$488k
NIAAA NIH HHS AA013890NIGMS NIH HHS GM59297
6 · The paper itself

Abstract

purposeTo determine whether R282 in transmembrane segment 7 (TMS7) of hPepT1 forms a salt bridge with D341 in TMS8.

methodsMutated hPepT1 transporters containing point mutations at R282 and/or D341 were transiently transfected into HEK293 cells. Their steady state expression and functional activity were measured using immunoprecipitation and 3H-gly-sar uptake, respectively. Gly-sar uptake by cysteine mutants (R282C and D341C) was also measured in the presence and absence of cysteine-modifying MTS reagents.

resultsThe reverse-charge mutants R282D-hPepT1 and D341R-hPepT1 showed significantly reduced gly-sar uptake, but the double mutant (R282D/D341R-hPepT1) has functionality comparable to that of wild-type hPepT1. Gly-sar uptake by R282C-hPepT1 is reduced, but pre-incubation with 1 mM MTSET, a positively charged cysteine-modifying reagent, restored function to wild-type levels. Similarly, pre-incubation of D341C-hPepT1 with 10 mM MTSES, a negatively charged cysteine-modifying reagent, increased gly-sar uptake compared to unmodified D341C-hPepT1. In contrast, MTSET modification of D341C-hPepT1 (giving a positive charge at position 341) resulted in significant reduction in gly-sar uptake, compared to D341C-hPepT1.

conclusionOur results are consistent with a salt bridge between R282 and D341 in hPepT1, and we use these and other data to propose a role for the R282-D341 charge pair in the hPepT1 translocation mechanism.

Indexed as

Amino Acid SubstitutionBlotting, WesternCell LineHumansImmunoprecipitationLuminescenceMutagenesis, Site-DirectedMutationPeptide Transporter 1SymportersTransfectionPeptide Transporter 1SLC15A1 protein, humanSymporters

Identifiers

PMID17009102
OpenAlexW2055032874

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.