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| | <StructureSection load='6ryo' size='340' side='right'caption='[[6ryo]], [[Resolution|resolution]] 1.92Å' scene=''> | | <StructureSection load='6ryo' size='340' side='right'caption='[[6ryo]], [[Resolution|resolution]] 1.92Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ryo]] 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=6RYO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RYO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ryo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RYO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RYO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7PE:2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL'>7PE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.924Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5BV:(2R,3R)-3-(GLYCYLOXY)-2-METHYLNONANOIC+ACID'>5BV</scene>, <scene name='pdbligand=ALO:ALLO-THREONINE'>ALO</scene>, <scene name='pdbligand=IIL:ISO-ISOLEUCINE'>IIL</scene>, <scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5BV:(2R,3R)-3-(GLYCYLOXY)-2-METHYLNONANOIC+ACID'>5BV</scene>, <scene name='pdbligand=7PE:2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL'>7PE</scene>, <scene name='pdbligand=ALO:ALLO-THREONINE'>ALO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IIL:ISO-ISOLEUCINE'>IIL</scene>, <scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lspA, lsp, SAR1172 ([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=6ryo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ryo OCA], [https://pdbe.org/6ryo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ryo RCSB], [https://www.ebi.ac.uk/pdbsum/6ryo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ryo 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/Signal_peptidase_II Signal peptidase II], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.36 3.4.23.36] </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=6ryo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ryo OCA], [http://pdbe.org/6ryo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ryo RCSB], [http://www.ebi.ac.uk/pdbsum/6ryo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ryo ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LSPA_STAAR LSPA_STAAR]] This protein specifically catalyzes the removal of signal peptides from prolipoproteins. | + | [https://www.uniprot.org/uniprot/LSPA_STAAR LSPA_STAAR] This protein specifically catalyzes the removal of signal peptides from prolipoproteins. |
| | <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: Signal peptidase II]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Bailey, J]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Caffrey, M]] | + | [[Category: Bailey J]] |
| - | [[Category: Huang, C Y]] | + | [[Category: Caffrey M]] |
| - | [[Category: Olatunji, S]] | + | [[Category: Huang CY]] |
| - | [[Category: Olieric, V]] | + | [[Category: Olatunji S]] |
| - | [[Category: Wang, M]] | + | [[Category: Olieric V]] |
| - | [[Category: Yu, X]] | + | [[Category: Wang M]] |
| - | [[Category: Globomycin]]
| + | [[Category: Yu X]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: In meso]]
| + | |
| - | [[Category: Lipid cubic phase]]
| + | |
| - | [[Category: Lipoprotein signal peptidase]]
| + | |
| Structural highlights
6ryo is a 2 chain structure with sequence from Staphylococcus aureus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.924Å |
| Ligands: | , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
LSPA_STAAR This protein specifically catalyzes the removal of signal peptides from prolipoproteins.
Publication Abstract from PubMed
Antimicrobial resistance is a major global threat that calls for new antibiotics. Globomycin and myxovirescin are two natural antibiotics that target the lipoprotein-processing enzyme, LspA, thereby compromising the integrity of the bacterial cell envelope. As part of a project aimed at understanding their mechanism of action and for drug development, we provide high-resolution crystal structures of the enzyme from the human pathogen methicillin-resistant Staphylococcus aureus (MRSA) complexed with globomycin and with myxovirescin. Our results reveal an instance of convergent evolution. The two antibiotics possess different molecular structures. Yet, they appear to inhibit identically as non-cleavable tetrahedral intermediate analogs. Remarkably, the two antibiotics superpose along nineteen contiguous atoms that interact similarly with LspA. This 19-atom motif recapitulates a part of the substrate lipoprotein in its proposed binding mode. Incorporating this motif into a scaffold with suitable pharmacokinetic properties should enable the development of effective antibiotics with built-in resistance hardiness.
Structures of lipoprotein signal peptidase II from Staphylococcus aureus complexed with antibiotics globomycin and myxovirescin.,Olatunji S, Yu X, Bailey J, Huang CY, Zapotoczna M, Bowen K, Remskar M, Muller R, Scanlan EM, Geoghegan JA, Olieric V, Caffrey M Nat Commun. 2020 Jan 9;11(1):140. doi: 10.1038/s41467-019-13724-y. PMID:31919415[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Olatunji S, Yu X, Bailey J, Huang CY, Zapotoczna M, Bowen K, Remskar M, Muller R, Scanlan EM, Geoghegan JA, Olieric V, Caffrey M. Structures of lipoprotein signal peptidase II from Staphylococcus aureus complexed with antibiotics globomycin and myxovirescin. Nat Commun. 2020 Jan 9;11(1):140. doi: 10.1038/s41467-019-13724-y. PMID:31919415 doi:http://dx.doi.org/10.1038/s41467-019-13724-y
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