View source for 6ryo


==Bacterial membrane enzyme structure by the in meso method at 1.9 A resolution==
<StructureSection load='6ryo' size='340' side='right'caption='[[6ryo]], [[Resolution|resolution]] 1.92&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.924&#8491;</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='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>
</table>
== Function ==
[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 6ryo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus]]
[[Category: Synthetic construct]]
[[Category: Bailey J]]
[[Category: Caffrey M]]
[[Category: Huang CY]]
[[Category: Olatunji S]]
[[Category: Olieric V]]
[[Category: Wang M]]
[[Category: Yu X]]