6gz9: Difference between revisions
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<StructureSection load='6gz9' size='340' side='right' caption='[[6gz9]], [[Resolution|resolution]] 3.10Å' scene=''> | <StructureSection load='6gz9' size='340' side='right' caption='[[6gz9]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6gz9]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GZ9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GZ9 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6gz9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_27844 Atcc 27844]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GZ9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GZ9 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TXC:2-[(2-AMINO-6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)METHOXY]ETHYL+L-VALINATE'>TXC</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TXC:2-[(2-AMINO-6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)METHOXY]ETHYL+L-VALINATE'>TXC</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BL313_09825 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1290 ATCC 27844])</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=6gz9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gz9 OCA], [http://pdbe.org/6gz9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gz9 RCSB], [http://www.ebi.ac.uk/pdbsum/6gz9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gz9 ProSAT]</span></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=6gz9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gz9 OCA], [http://pdbe.org/6gz9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gz9 RCSB], [http://www.ebi.ac.uk/pdbsum/6gz9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gz9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A major challenge in drug development is the optimization of intestinal absorption and cellular uptake. A successful strategy has been to develop prodrug molecules, which hijack solute carrier (SLC) transporters for active transport into the body. The proton-coupled oligopeptide transporters, PepT1 and PepT2, have been successfully targeted using this approach. Peptide transporters display a remarkable capacity to recognize a diverse library of di- and tripeptides, making them extremely promiscuous and major contributors to the pharmacokinetic profile of several important drug classes, including beta-lactam antibiotics and antiviral and antineoplastic agents. Of particular interest has been their ability to recognize amino acid and peptide-based prodrug molecules, thereby providing a rational approach to improving drug transport into the body. However, the structural basis for prodrug recognition has remained elusive. Here we present crystal structures of a prokaryotic homolog of the mammalian transporters in complex with the antiviral prodrug valacyclovir and the peptide-based photodynamic therapy agent, 5-aminolevulinic acid. The valacyclovir structure reveals that prodrug recognition is mediated through both the amino acid scaffold and the ester bond, which is commonly used to link drug molecules to the carrier's physiological ligand, whereas 5-aminolevulinic acid makes far fewer interactions compared with physiological peptides. These structures provide a unique insight into how peptide transporters interact with xenobiotic molecules and provide a template for further prodrug development. | |||
Structural basis for prodrug recognition by the SLC15 family of proton-coupled peptide transporters.,Minhas GS, Newstead S Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):804-809. doi:, 10.1073/pnas.1813715116. Epub 2019 Jan 2. PMID:30602453<ref>PMID:30602453</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6gz9" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Atcc 27844]] | |||
[[Category: Minhas, G S]] | [[Category: Minhas, G S]] | ||
[[Category: Newstead, S]] | [[Category: Newstead, S]] | ||