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<StructureSection load='6ryp' size='340' side='right'caption='[[6ryp]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='6ryp' size='340' side='right'caption='[[6ryp]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6ryp]] is a 1 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=6RYP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RYP FirstGlance]. <br>
<table><tr><td colspan='2'>[[6ryp]] is a 1 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=6RYP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RYP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KNH:Myxovirescin+A'>KNH</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.3&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KNH:Myxovirescin+A'>KNH</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6ryp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ryp OCA], [https://pdbe.org/6ryp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ryp RCSB], [https://www.ebi.ac.uk/pdbsum/6ryp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ryp 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=6ryp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ryp OCA], [http://pdbe.org/6ryp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ryp RCSB], [http://www.ebi.ac.uk/pdbsum/6ryp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ryp 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;">
== 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<ref>PMID:31919415</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ryp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Signal peptidase II]]
[[Category: Staphylococcus aureus]]
[[Category: Bailey, J]]
[[Category: Bailey J]]
[[Category: Caffrey, M]]
[[Category: Caffrey M]]
[[Category: Huang, C Y]]
[[Category: Huang CY]]
[[Category: Olatunji, S]]
[[Category: Olatunji S]]
[[Category: Olieric, V]]
[[Category: Olieric V]]
[[Category: Wang, M]]
[[Category: Wang M]]
[[Category: Yu, X]]
[[Category: Yu X]]
[[Category: Hydrolase]]
[[Category: In meso]]
[[Category: Lipid cubic phase]]
[[Category: Lipoprotein signal peptidase]]
[[Category: Myxovirescin]]

Latest revision as of 07:37, 1 May 2024

Bacterial membrane enzyme structure by the in meso method at 2.3 A resolution

6ryp, resolution 2.30Å

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