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| | <StructureSection load='7l0a' size='340' side='right'caption='[[7l0a]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='7l0a' size='340' side='right'caption='[[7l0a]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7l0a]] is a 2 chain structure with sequence from [https://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=7L0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L0A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7l0a]] 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=7L0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L0A FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DD547_02660, DQV53_15175, EP54_00010, EQ90_02595, G0V24_06825, G0Z18_09875, G6Y10_06490, GO746_05055, GO803_04470, GO805_09630, GO821_02780, GO894_07900, GO942_11740, HMPREF2819_04260, HMPREF3211_01237, NCTC10654_02801, NCTC10702_04070, NCTC10988_03042, RK64_00235 ([https://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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/S-formylglutathione_hydrolase S-formylglutathione hydrolase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.12 3.1.2.12] </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=7l0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l0a OCA], [https://pdbe.org/7l0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l0a RCSB], [https://www.ebi.ac.uk/pdbsum/7l0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l0a 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=7l0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l0a OCA], [https://pdbe.org/7l0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l0a RCSB], [https://www.ebi.ac.uk/pdbsum/7l0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l0a ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q2FUY3_STAA8 Q2FUY3_STAA8] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: S-formylglutathione hydrolase]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Jez, J M]] | + | [[Category: Jez JM]] |
| - | [[Category: John, A R.Odom]]
| + | [[Category: Miller JJ]] |
| - | [[Category: Miller, J J]] | + | [[Category: Odom John AR]] |
| - | [[Category: Frmb]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
Q2FUY3_STAA8
Publication Abstract from PubMed
Carboxy ester prodrugs are widely employed to increase oral absorption and potency of phosphonate antibiotics. Prodrugging can mask problematic chemical features that prevent cellular uptake and may enable tissue-specific compound delivery. However, many carboxy ester promoieties are rapidly hydrolyzed by serum esterases, limiting their therapeutic potential. While carboxy ester-based prodrug targeting is feasible, it has seen limited use in microbes as microbial esterase-specific promoieties have not been described. Here we identify the bacterial esterases, GloB and FrmB, that activate carboxy ester prodrugs in Staphylococcus aureus. Additionally, we determine the substrate specificities for FrmB and GloB and demonstrate the structural basis of these preferences. Finally, we establish the carboxy ester substrate specificities of human and mouse sera, ultimately identifying several promoieties likely to be serum esterase-resistant and microbially labile. These studies will enable structure-guided design of antistaphylococcal promoieties and expand the range of molecules to target staphylococcal pathogens.
Structure-guided microbial targeting of antistaphylococcal prodrugs.,Miller JJ, Shah IT, Hatten J, Barekatain Y, Mueller EA, Moustafa AM, Edwards RL, Dowd CS, Planet PJ, Muller FL, Jez JM, Odom John AR Elife. 2021 Jul 19;10. pii: 66657. doi: 10.7554/eLife.66657. PMID:34279224[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Miller JJ, Shah IT, Hatten J, Barekatain Y, Mueller EA, Moustafa AM, Edwards RL, Dowd CS, Planet PJ, Muller FL, Jez JM, Odom John AR. Structure-guided microbial targeting of antistaphylococcal prodrugs. Elife. 2021 Jul 19;10. pii: 66657. doi: 10.7554/eLife.66657. PMID:34279224 doi:http://dx.doi.org/10.7554/eLife.66657
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