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| | <StructureSection load='6gs7' size='340' side='right'caption='[[6gs7]], [[Resolution|resolution]] 3.30Å' scene=''> | | <StructureSection load='6gs7' size='340' side='right'caption='[[6gs7]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6gs7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli] and [http://en.wikipedia.org/wiki/Lama Lama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GS7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GS7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6gs7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GS7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GS7 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dtpA, tppB, ydgR, b1634, JW1626 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gs7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gs7 OCA], [http://pdbe.org/6gs7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gs7 RCSB], [http://www.ebi.ac.uk/pdbsum/6gs7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gs7 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6gs7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gs7 OCA], [https://pdbe.org/6gs7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gs7 RCSB], [https://www.ebi.ac.uk/pdbsum/6gs7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gs7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DTPA_ECOLI DTPA_ECOLI]] Proton-dependent permease that transports di- and tripeptides as well as structurally related peptidomimetics such as aminocephalosporins into the cell. Has a clear preference for dipeptides and tripeptides composed of L-amino acids, and discriminates dipeptides on the basis of the position of charges within the substrate.<ref>PMID:15175316</ref> <ref>PMID:17158458</ref> <ref>PMID:18485005</ref> | + | [https://www.uniprot.org/uniprot/DTPA_ECOLI DTPA_ECOLI] Proton-dependent permease that transports di- and tripeptides as well as structurally related peptidomimetics such as aminocephalosporins into the cell. Has a clear preference for dipeptides and tripeptides composed of L-amino acids, and discriminates dipeptides on the basis of the position of charges within the substrate.<ref>PMID:15175316</ref> <ref>PMID:17158458</ref> <ref>PMID:18485005</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Lama]] | + | [[Category: Lama glama]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Flayhan, A]] | + | [[Category: Flayhan A]] |
| - | [[Category: Loew, C]] | + | [[Category: Loew C]] |
| - | [[Category: Quistgaard, E M]] | + | [[Category: Quistgaard EM]] |
| - | [[Category: Ural-Blimke, Y]] | + | [[Category: Ural-Blimke Y]] |
| - | [[Category: Complex with nanobody]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Peptide transporter]]
| + | |
| - | [[Category: Slc15 family member]]
| + | |
| Structural highlights
Function
DTPA_ECOLI Proton-dependent permease that transports di- and tripeptides as well as structurally related peptidomimetics such as aminocephalosporins into the cell. Has a clear preference for dipeptides and tripeptides composed of L-amino acids, and discriminates dipeptides on the basis of the position of charges within the substrate.[1] [2] [3]
Publication Abstract from PubMed
Members of the solute carrier 15 family (SLC15) transport di- and tripeptides as well as peptidomimetic drugs across the cell membrane. Structures of bacterial homologues have provided valuable information on the binding and transport of their natural substrates, but many do not transport medically relevant drugs. In contrast, a homologue from Escherichia coli, DtpA, shows a high similarity to human PepT1 (SLC15A1) in terms of ligand selectivity and transports a similar set of drugs. Here, we present the crystal structure of DtpA in ligand-free form (at 3.30 A resolution) and in complex with the antiviral prodrug valganciclovir (at 2.65 A resolution) supported by biochemical data. We show that valganciclovir unexpectedly binds with the ganciclovir moiety mimicking the N-terminal residue of a canonical peptide substrate. Based on a homology model we argue that this binding mode also applies to the human PepT1 transporter. Our results provide new insights into the binding mode of prodrugs and will assist the rational design of drugs with improved absorption rates.
Structure of Prototypic Peptide Transporter DtpA from E. coli in Complex with Valganciclovir Provides Insights into Drug Binding of Human PepT1.,Ural-Blimke Y, Flayhan A, Strauss J, Rantos V, Bartels K, Nielsen R, Pardon E, Steyaert J, Kosinski J, Quistgaard EM, Low C J Am Chem Soc. 2019 Jan 15. doi: 10.1021/jacs.8b11343. PMID:30644743[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Goh EB, Siino DF, Igo MM. The Escherichia coli tppB (ydgR) gene represents a new class of OmpR-regulated genes. J Bacteriol. 2004 Jun;186(12):4019-24. doi: 10.1128/JB.186.12.4019-4024.2004. PMID:15175316 doi:http://dx.doi.org/10.1128/JB.186.12.4019-4024.2004
- ↑ Weitz D, Harder D, Casagrande F, Fotiadis D, Obrdlik P, Kelety B, Daniel H. Functional and structural characterization of a prokaryotic peptide transporter with features similar to mammalian PEPT1. J Biol Chem. 2007 Feb 2;282(5):2832-9. Epub 2006 Dec 8. PMID:17158458 doi:http://dx.doi.org/M604866200
- ↑ Harder D, Stolz J, Casagrande F, Obrdlik P, Weitz D, Fotiadis D, Daniel H. DtpB (YhiP) and DtpA (TppB, YdgR) are prototypical proton-dependent peptide transporters of Escherichia coli. FEBS J. 2008 Jul;275(13):3290-8. doi: 10.1111/j.1742-4658.2008.06477.x. Epub 2008, May 15. PMID:18485005 doi:http://dx.doi.org/10.1111/j.1742-4658.2008.06477.x
- ↑ Ural-Blimke Y, Flayhan A, Strauss J, Rantos V, Bartels K, Nielsen R, Pardon E, Steyaert J, Kosinski J, Quistgaard EM, Low C. Structure of Prototypic Peptide Transporter DtpA from E. coli in Complex with Valganciclovir Provides Insights into Drug Binding of Human PepT1. J Am Chem Soc. 2019 Jan 15. doi: 10.1021/jacs.8b11343. PMID:30644743 doi:http://dx.doi.org/10.1021/jacs.8b11343
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