Faculty Opinions recommendation of Proton movement and coupling in the POT family of peptide transporters.

The brush-border membrane of renal epithelial cells contains PEPT1 and PEPT2 proteins that are rheogenic carriers for short-chain peptides. The carrier proteins display a distinct surface expression pattern along the proximal tubule, suggesting that initially di- and tripeptides, either filtered or released by surface-bound hydrolases from larger oligopeptides, are taken up by the low-affinity but high-capacity PEPT1 transporter and then by PEPT2, which possesses a higher affinity but lower transport capacity. Both carriers transport essentially all possible di- and tripeptides and numerous structurally related drugs. A unique feature of the mammalian peptide transporters is the capability of proton-dependent electrogenic cotransport of all substrates, regardless of their charge, that is achieved by variable coupling in proton movement along with the substrate down the transmembrane potential difference. This review focuses on the postcloning research efforts to understand the molecular physiology of peptide transport processes in renal tubules and summarizes available data on the underlying genes, protein structures, and transporter function as derived from studies in heterologous expression systems.

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Proton movement and coupling in the POT family of peptide transporters

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1710727114 ◽

2017 ◽

Vol 114 (50) ◽

pp. 13182-13187 ◽

Cited By ~ 34

Author(s):

Joanne L. Parker ◽

Chenghan Li ◽

Allete Brinth ◽

Zhi Wang ◽

Lutz Vogeley ◽

...

Keyword(s):

Transport Systems ◽

Coupled Transport ◽

Defense Compounds ◽

Proton Binding ◽

Peptide Transporters ◽

The Family ◽

Peptide Binding Site ◽

Extracellular Side ◽

Proton Movement ◽

Dynamics Simulations

POT transporters represent an evolutionarily well-conserved family of proton-coupled transport systems in biology. An unusual feature of the family is their ability to couple the transport of chemically diverse ligands to an inwardly directed proton electrochemical gradient. For example, in mammals, fungi, and bacteria they are predominantly peptide transporters, whereas in plants the family has diverged to recognize nitrate, plant defense compounds, and hormones. Although recent structural and biochemical studies have identified conserved sites of proton binding, the mechanism through which transport is coupled to proton movement remains enigmatic. Here we show that different POT transporters operate through distinct proton-coupled mechanisms through changes in the extracellular gate. A high-resolution crystal structure reveals the presence of ordered water molecules within the peptide binding site. Multiscale molecular dynamics simulations confirm proton transport occurs through these waters via Grotthuss shuttling and reveal that proton binding to the extracellular side of the transporter facilitates a reorientation from an inward- to outward-facing state. Together these results demonstrate that within the POT family multiple mechanisms of proton coupling have likely evolved in conjunction with variation of the extracellular gate.

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Decreased Expression of Glucose and Peptide Transporters in Rat Remnant Kidney

Drug Metabolism and Pharmacokinetics ◽

10.2133/dmpk.19.41 ◽

2004 ◽

Vol 19 (1) ◽

pp. 41-47 ◽

Cited By ~ 23

Author(s):

Nobuhiko Nakamura ◽

Satohiro Masuda ◽

Kazushige Takahashi ◽

Hideyuki Saito ◽

Masahiro Okuda ◽

...

Keyword(s):

Peptide Transporters ◽

Remnant Kidney

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Dielectric Loss in Vanadyl Pnictates

MRS Proceedings ◽

10.1557/proc-210-681 ◽

1990 ◽

Vol 210 ◽

Cited By ~ 1

Author(s):

Joseph F. Lomax ◽

John J. Fontanella ◽

Mary C. Wintersgill ◽

Anthony Kotarski

Keyword(s):

Dielectric Loss ◽

Complex Impedance ◽

Audio Frequency ◽

Vanadyl Phosphate ◽

Nonstoichiometric Compound ◽

Proton Movement ◽

Related Compounds ◽

Water Species ◽

Acid Nature ◽

Chemical Evidence

AbstractThe results of audio frequency complex impedance studies for vanadyl phosphate and its hydrates (VOPO4*nH2O;n=0,1,2) are reported. Measurements were made at seventeen frequencies between 10 and 105 Hz over the temperature range 5.5-380K. Two lowtemperature features were observed and are correlated with particular water species between the VOPO4 layers. In light of chemical evidence and compleximpedance measurements on related compounds, it is speculated that VOPCO4*nH2O (Pc = P, As) can be thought of as a mixed nonstoichiometric compound [VO(HPcO4)]x[VOPcO4O4]1-x*nH2O and the solid Brϕnsted acid nature of the compound is related to proton movement between layer pnictates and intralayer waters.

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Comparison of Human and Monkey Peptide Transporters: PEPT1 and PEPT2

Molecular Pharmaceutics ◽

10.1021/mp0499712 ◽

2004 ◽

Vol 1 (3) ◽

pp. 201-210 ◽

Cited By ~ 22

Author(s):

Eric Y. Zhang ◽

Richard M. Emerick ◽

Youngeen A. Pak ◽

Steven A. Wrighton ◽

Kathleen M. Hillgren

Keyword(s):

Peptide Transporters

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A new assay for nitric oxide reductase reveals two conserved glutamate residues form the entrance to a proton-conducting channel in the bacterial enzyme

Biochemical Journal ◽

10.1042/bj20060856 ◽

2006 ◽

Vol 401 (1) ◽

pp. 111-119 ◽

Cited By ~ 47

Author(s):

Faye H. Thorndycroft ◽

Gareth Butland ◽

David J. Richardson ◽

Nicholas J. Watmough

Keyword(s):

Nitric Oxide ◽

Paracoccus Denitrificans ◽

Nitric Oxide Reductase ◽

Transmembrane Helices ◽

Level Of Activity ◽

Bacterial Enzyme ◽

Cytoplasmic Membranes ◽

Membrane Bound ◽

Proton Movement ◽

High Level

A specific amperometric assay was developed for the membrane-bound NOR [NO (nitric oxide) reductase] from the model denitrifying bacterium Paracoccus denitrificans using its natural electron donor, pseudoazurin, as a co-substrate. The method allows the rapid and specific assay of NO reduction catalysed by recombinant NOR expressed in the cytoplasmic membranes of Escherichia coli. The effect on enzyme activity of substituting alanine, aspartate or glutamine for two highly conserved glutamate residues, which lie in a periplasmic facing loop between transmembrane helices III and IV in the catalytic subunit of NOR, was determined using this method. Three of the substitutions (E122A, E125A and E125D) lead to an almost complete loss of NOR activity. Some activity is retained when either Glu122 or Glu125 is substituted with a glutamine residue, but only replacement of Glu122 with an aspartate residue retains a high level of activity. These results are interpreted in terms of these residues forming the mouth of a channel that conducts substrate protons to the active site of NOR during turnover. This channel is also likely to be that responsible in the coupling of proton movement to electron transfer during the oxidation of fully reduced NOR with oxygen [U. Flock, N. J. Watmough and P. Ädelroth (2005) Biochemistry 44, 10711–10719].

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OLECULAR AND CELL BIOLOGICAL ANALYSES OF DRUG RECOGNITION BY RAT PEPTIDE TRANSPORTERS

Drug Metabolism and Pharmacokinetics ◽

10.2133/dmpk.12.supplement_82 ◽

1997 ◽

Vol 12 (supplement) ◽

pp. 82-83

Author(s):

Tomohiro TERADA ◽

Kazushige TAKAHASHI ◽

Nobuhiko NAKAMURA ◽

Hideyuki SAITO ◽

Ken-ichi INUI

Keyword(s):

Peptide Transporters

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NPF genes excavation and their expression response to vernalization and nitrogen deficiency in allotetraploid rapeseed

10.21203/rs.3.rs-236072/v1 ◽

2021 ◽

Author(s):

Hongbo Chao ◽

Jianjie He ◽

Weiguo Zhao ◽

Hong Fu ◽

Yingpeng Hua ◽

...

Keyword(s):

Expression Patterns ◽

Functional Characterization ◽

Nitrogen Deficiency ◽

Enrichment Analysis ◽

Functional Differentiation ◽

Peptide Transporter ◽

Peptide Transporters ◽

Transporter Family ◽

Expression Response ◽

Metabolite Content

Abstract Background The NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER FAMILY (NPF) genes, initially characterized as nitrate or peptide transporters in plants, involve in the transport of a large variety of substrates including amino acids, nitrate, auxin (IAA), jasmonates (JAs), abscisic acid (ABA) and gibberellins (GAs) and glucosinolates. The evolution and expression diversification of genes determine their functional differentiation in polyploid species. Results Among 169 NPF genes excavated in Brassica napus, 97 B. napus NPF (BnaNPF) genes evolved from B. rapa, and 72 BnaNPF genes from B. olereaca. They unevenly distributed on B. napus genome and exhibited obvious synteny with NPF genes in Arabidopsis thaliana, B. rapa and B. olereaca. BnaNPF genes were identified to show diversified expression patterns in 90 different organs or tissues based on transcriptome profile data. Besides, they exhibited complex expression changes in the development process of leaves, silique wall and seeds, which indicated that the expression of BnaNPF genes maybe respond to altered phytohormone and secondary metabolite content through combining with promoter elements enrichment analysis. Furthermore, many BnaNPF genes were detected to response to vernalization with two different patterns and 20 BnaNPF genes responded to nitrate deficiency. Conclusion The evolution of BnaNPF genes and their expression pattern including response to vernalization and nitrogen deficiency were characterized and provide valuable information for further functional characterization in rapeseed.

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