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Philos Trans R Soc Lond B Biol Sci
2009 Jan 27;3641514:203-7. doi: 10.1098/rstb.2008.0139.
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Review. The mammalian proton-coupled peptide cotransporter PepT1: sitting on the transporter-channel fence?
Meredith D
.
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The proton-coupled di- and tripeptide transporter PepT1 (SLC15a1) is the major route by which dietary nitrogen is taken up from the small intestine, as well as being the route of entry for important therapeutic (pro)drugs such as the beta-lactam antibiotics, angiotensin-converting enzyme inhibitors and antiviral and anti-cancer agents. PepT1 is a member of the major facilitator superfamily of 12 transmembrane domain transporter proteins. Expression studies in Xenopus laevis on rabbit PepT1 that had undergone site-directed mutagenesis of a conserved arginine residue (arginine282 in transmembrane domain 7) to a glutamate revealed that this residue played a role in the coupling of proton and peptide transport and prevented the movement of non-coupled ions during the transporter cycle. Mutations of arginine282 to other non-positive residues did not uncouple proton-peptide cotransport, but did allow additional ion movements when substrate was added. By contrast, mutations to positive residues appeared to function the same as wild-type. These findings are discussed in relation to the functional role that arginine282 may play in the way PepT1 operates, together with structural information from the homology model of PepT1 based on the Escherichia coli lactose permease crystal structure.
Figure 1. Helical wheel plan of the TMDs in PepT1 showing the putative relative proximity of H57, R282 and D341 in the TMDs 2, 7 and 8, respectively, in the homology model of rabbit PepT1 (modified from Meredith & Price 2006).
Abramson,
Structural comparison of lactose permease and the glycerol-3-phosphate antiporter: members of the major facilitator superfamily.
2004, Pubmed
Abramson,
Structural comparison of lactose permease and the glycerol-3-phosphate antiporter: members of the major facilitator superfamily.
2004,
Pubmed
Bailey,
How to Make Drugs Orally Active: A Substrate Template for Peptide Transporter PepT1.
2000,
Pubmed
Bailey,
Affinity prediction for substrates of the peptide transporter PepT1.
2006,
Pubmed
Biegel,
Three-dimensional quantitative structure-activity relationship analyses of beta-lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide cotransporter PEPT1.
2005,
Pubmed
Biegel,
The renal type H+/peptide symporter PEPT2: structure-affinity relationships.
2006,
Pubmed
Bolger,
Structure, function, and molecular modeling approaches to the study of the intestinal dipeptide transporter PepT1.
1998,
Pubmed
Borre,
Arginine 445 controls the coupling between glutamate and cations in the neuronal transporter EAAC-1.
2004,
Pubmed
Bruce,
Monovalent cation leaks in human red cells caused by single amino-acid substitutions in the transport domain of the band 3 chloride-bicarbonate exchanger, AE1.
2005,
Pubmed
,
Xenbase
Covitz,
Membrane topology of the human dipeptide transporter, hPEPT1, determined by epitope insertions.
1998,
Pubmed
Daniel,
The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology.
2004,
Pubmed
Fei,
Expression cloning of a mammalian proton-coupled oligopeptide transporter.
1994,
Pubmed
,
Xenbase
Kaback,
The kamikaze approach to membrane transport.
2001,
Pubmed
Kulkarni,
Analysis of transmembrane segment 7 of the dipeptide transporter hPepT1 by cysteine-scanning mutagenesis.
2003,
Pubmed
Kulkarni,
A charge pair interaction between Arg282 in transmembrane segment 7 and Asp341 in transmembrane segment 8 of hPepT1.
2007,
Pubmed
Liang,
Human intestinal H+/peptide cotransporter. Cloning, functional expression, and chromosomal localization.
1995,
Pubmed
,
Xenbase
Martial,
Consequences of point mutations in trout anion exchanger 1 (tAE1) transmembrane domains: evidence that tAE1 can behave as a chloride channel.
2006,
Pubmed
,
Xenbase
Meredith,
Molecular modeling of PepT1--towards a structure.
2006,
Pubmed
Meredith,
Site-directed mutation of arginine 282 to glutamate uncouples the movement of peptides and protons by the rabbit proton-peptide cotransporter PepT1.
2004,
Pubmed
,
Xenbase
Meredith,
Oligopeptide transport by epithelial cells.
1995,
Pubmed
Meredith,
Structure and function of eukaryotic peptide transporters.
2000,
Pubmed
Meredith,
4-aminomethylbenzoic acid is a non-translocated competitive inhibitor of the epithelial peptide transporter PepT1.
1998,
Pubmed
,
Xenbase
Panitsas,
Evidence that the rabbit proton-peptide co-transporter PepT1 is a multimer when expressed in Xenopus laevis oocytes.
2006,
Pubmed
,
Xenbase
Pieri,
Site-directed mutagenesis of Arginine282 suggests how protons and peptides are co-transported by rabbit PepT1.
2008,
Pubmed
,
Xenbase
Saier,
TCDB: the Transporter Classification Database for membrane transport protein analyses and information.
2006,
Pubmed
Temple,
A model for the kinetics of neutral and anionic dipeptide-proton cotransport by the apical membrane of rat kidney cortex.
1996,
Pubmed
Temple,
Substrate-charge dependence of stoichiometry shows membrane potential is the driving force for proton-peptide cotransport in rat renal cortex.
1995,
Pubmed
Terada,
Peptide transporters: structure, function, regulation and application for drug delivery.
2004,
Pubmed
Vig,
Human PEPT1 pharmacophore distinguishes between dipeptide transport and binding.
2006,
Pubmed
