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| | <StructureSection load='5ets' size='340' side='right'caption='[[5ets]], [[Resolution|resolution]] 1.95Å' scene=''> | | <StructureSection load='5ets' size='340' side='right'caption='[[5ets]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ets]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ETS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5ETS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ets]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ETS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ETS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5RX:2-AZANYL-8-[(4-CHLOROPHENYL)METHYLSULFANYL]-1,9-DIHYDROPURIN-6-ONE'>5RX</scene>, <scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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]] 1.95Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5etn|5etn]], [[5etk|5etk]], [[5etl|5etl]], [[5etm|5etm]], [[5eto|5eto]], [[5etp|5etp]], [[5etq|5etq]], [[5etr|5etr]], [[5ett|5ett]], [[5etv|5etv]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5RX:2-AZANYL-8-[(4-CHLOROPHENYL)METHYLSULFANYL]-1,9-DIHYDROPURIN-6-ONE'>5RX</scene>, <scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RK60_02090, RK67_01645, RK72_06915, RK74_04210, RK75_00240, RK80_01970, RK83_05435, RK84_03130, RK95_04415, RK96_04825, RK98_03440, RK99_07885, RL05_10010, RL06_09555, RL08_05305, TM59_02255 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</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=5ets FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ets OCA], [https://pdbe.org/5ets PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ets RCSB], [https://www.ebi.ac.uk/pdbsum/5ets PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ets ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/2-amino-4-hydroxy-6-hydroxymethyldihydropteridine_diphosphokinase 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.6.3 2.7.6.3] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ets FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ets OCA], [http://pdbe.org/5ets PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ets RCSB], [http://www.ebi.ac.uk/pdbsum/5ets PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ets ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q2G0Q5_STAA8 Q2G0Q5_STAA8] |
| | <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: 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dennis, M L]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Peat, T S]] | + | [[Category: Dennis ML]] |
| - | [[Category: Swarbrick, J D]] | + | [[Category: Peat TS]] |
| - | [[Category: Ampcpp]] | + | [[Category: Swarbrick JD]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Pyrophosphokinase]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| Structural highlights
Function
Q2G0Q5_STAA8
Publication Abstract from PubMed
6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is a member of the folate biosynthesis pathway found in prokaryotes and lower eukaryotes that catalyzes the pyrophosphoryl transfer from the ATP cofactor to a 6-hydroxymethyl-7,8-dihydropterin substrate. We report the chemical synthesis of a series of S-functionalized 8-mercaptoguanine (8MG) analogues as substrate site inhibitors of HPPK and quantify binding against the E. coli and S. aureus enzymes (EcHPPK and SaHPPK). The results demonstrate that analogues incorporating acetophenone-based substituents have comparable affinities for both enzymes. Preferential binding of benzyl-substituted 8MG derivatives to SaHPPK was reconciled when a cryptic pocket unique to SaHPPK was revealed by X-ray crystallography. Differential chemical shift perturbation analysis confirmed this to be a common mode of binding for this series to SaHPPK. One compound (41) displayed binding affinities of 120 nM and 1.76 muM for SaHPPK and EcHPPK, respectively, and represents a lead for the development of more potent and selective inhibitors of SaHPPK.
Structural Basis for the Selective Binding of Inhibitors to 6-Hydroxymethyl-7,8-dihydropterin Pyrophosphokinase from Staphylococcus aureus and Escherichia coli.,Dennis ML, Pitcher NP, Lee MD, DeBono AJ, Wang ZC, Harjani JR, Rahmani R, Cleary B, Peat TS, Baell JB, Swarbrick JD J Med Chem. 2016 Apr 26. PMID:27094768[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dennis ML, Pitcher NP, Lee MD, DeBono AJ, Wang ZC, Harjani JR, Rahmani R, Cleary B, Peat TS, Baell JB, Swarbrick JD. Structural Basis for the Selective Binding of Inhibitors to 6-Hydroxymethyl-7,8-dihydropterin Pyrophosphokinase from Staphylococcus aureus and Escherichia coli. J Med Chem. 2016 Apr 26. PMID:27094768 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b00002
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