5u13: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==E. coli dihydropteroate synthase complexed with an 8-mercaptoguanine derivative: 2-amino-8-{[2-(4-methoxyphenyl)-2-oxoethyl]sulfanyl}-1,7-dihydro-6H-purin-6-one== | ==E. coli dihydropteroate synthase complexed with an 8-mercaptoguanine derivative: 2-amino-8-{[2-(4-methoxyphenyl)-2-oxoethyl]sulfanyl}-1,7-dihydro-6H-purin-6-one== | ||
<StructureSection load='5u13' size='340' side='right' caption='[[5u13]], [[Resolution|resolution]] 1.95Å' scene=''> | <StructureSection load='5u13' size='340' side='right'caption='[[5u13]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5u13]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5u13]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_CFT073 Escherichia coli CFT073]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U13 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U13 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.951Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YH5:2-AMINO-8-{[2-(4-METHOXYPHENYL)-2-OXOETHYL]SULFANYL}-1,9-DIHYDRO-6H-PURIN-6-ONE'>YH5</scene></td></tr> | |||
<tr id=' | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5u13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u13 OCA], [https://pdbe.org/5u13 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u13 RCSB], [https://www.ebi.ac.uk/pdbsum/5u13 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u13 ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/DHPS_ECOLI DHPS_ECOLI] DHPS catalyzes the formation of the immediate precursor of folic acid. It is implicated in resistance to sulfonamide.<ref>PMID:368012</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 21: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5u13" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5u13" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Dihydropteroate synthase 3D structures|Dihydropteroate synthase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli CFT073]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Dennis | [[Category: Dennis ML]] | ||
[[Category: Peat | [[Category: Peat TS]] | ||
[[Category: Swarbrick | [[Category: Swarbrick JD]] | ||
Latest revision as of 16:18, 4 October 2023
E. coli dihydropteroate synthase complexed with an 8-mercaptoguanine derivative: 2-amino-8-{[2-(4-methoxyphenyl)-2-oxoethyl]sulfanyl}-1,7-dihydro-6H-purin-6-oneE. coli dihydropteroate synthase complexed with an 8-mercaptoguanine derivative: 2-amino-8-{[2-(4-methoxyphenyl)-2-oxoethyl]sulfanyl}-1,7-dihydro-6H-purin-6-one
Structural highlights
FunctionDHPS_ECOLI DHPS catalyzes the formation of the immediate precursor of folic acid. It is implicated in resistance to sulfonamide.[1] Publication Abstract from PubMedDihydropteroate synthase (DHPS) is an enzyme of the folate biosynthesis pathway which catalyzes the formation of 7,8-dihydropteroate (DHPt) from 6-hydroxymethyl-7,8-dihydropterin pyrophosphate (DHPPP) and para-aminobenzoic acid (pABA). DHPS is the long-standing target of the sulfonamide class of antibiotics that compete with pABA. In the wake of sulfa drug resistance, targeting the structurally rigid (and more conserved) pterin site has been proposed as an alternate strategy to inhibit DHPS in wild-type and sulfa drug resistant strains. Following work developing pterin-site inhibitors of the adjacent enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), we now present derivatives of 8-mercaptoguanine, a fragment that binds weakly within both enzymes, and quantify sub-muM binding using Surface Plasmon Resonance (SPR) to Escherichia coli DHPS (EcDHPS). Eleven ligand-bound EcDHPS crystal structures delineate the structure-activity relationship observed providing a structural framework for the rational development of novel, substrate envelope-compliant DHPS inhibitors. 8-Mercaptoguanine derivatives as inhibitors of dihydropteroate synthase.,Swarbrick J, Dennis M, Lee M, Harjani J, Ahmed M, Debono A, Pitcher N, Wang ZC, Chhabra S, Barlow N, Rahmani R, Cleary B, Dolezal O, Hattarki M, Aurelio L, Shonberg J, Graham B, Peat T, Baell J Chemistry. 2017 Nov 24. doi: 10.1002/chem.201704730. PMID:29171692[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||