View source for 6ewz


==Crystal structure of RelP (SAS2) from Staphylococcus aureus bound to AMPCPP and GTP in the pre-catalytic state==
<StructureSection load='6ewz' size='340' side='right' caption='[[6ewz]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ewz]] 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=6EWZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EWZ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ywaC, BER48_002454, CEJ93_03805, ERS072738_01254, ERS073583_01544, ERS074020_00750, HMPREF3211_00175 ([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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/GTP_diphosphokinase GTP diphosphokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.6.5 2.7.6.5] </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=6ewz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ewz OCA], [http://pdbe.org/6ewz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ewz RCSB], [http://www.ebi.ac.uk/pdbsum/6ewz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ewz ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The stringent response is a global reprogramming of bacterial physiology that renders cells more tolerant to antibiotics and induces virulence gene expression in pathogens in response to stress. This process is driven by accumulation of the intracellular alarmone guanosine-5'-di(tri)phosphate-3'-diphosphate ([p]ppGpp), which is produced by enzymes of the RelA SpoT homologue (RSH) family. The Gram-positive Firmicute pathogen, Staphylococcus aureus, encodes three RSH enzymes: a multi-domain RSH (Rel) that senses amino acid starvation on the ribosome and two small alarmone synthetase (SAS) enzymes, RelQ (SAS1) and RelP (SAS2). In Bacillus subtilis, RelQ (SAS1) was shown to form a tetramer that is activated by pppGpp and inhibited by single stranded RNA, but the structural and functional regulation of RelP (SAS2) is unexplored. Here, we present crystal structures of S. aureus RelP in two major functional states, pre-catalytic (bound to GTP and the non-hydrolyzable ATP analogue, AMPCPP) and post-catalytic (bound to pppGpp). We observed that RelP also forms a tetramer, but unlike RelQ (SAS1), it is strongly inhibited by both pppGpp and ppGpp and is insensitive to inhibition by RNA. We also identified putative metal ion-binding sites at the subunit interfaces that were consistent with the observed activation of the enzyme by Zn(2+) ions. The structures reported here reveal the details of the catalytic mechanism of SAS enzymes and provide a molecular basis for understanding differential regulation of SAS enzymes in Firmicute bacteria.

Structural basis for (p)ppGpp synthesis by the Staphylococcus aureus small alarmone synthetase RelP.,Manav MC, Beljantseva J, Bojer MS, Tenson T, Ingmer H, Hauryliuk V, Brodersen DE J Biol Chem. 2018 Jan 11. pii: RA117.001374. doi: 10.1074/jbc.RA117.001374. PMID:29326162<ref>PMID:29326162</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ewz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: GTP diphosphokinase]]
[[Category: Brodersen, D E]]
[[Category: Manav, M C]]
[[Category: Magic spot]]
[[Category: Mrsa]]
[[Category: Persistence]]
[[Category: Resistance]]
[[Category: Small alarmone synthetase]]
[[Category: Staphylococcus]]
[[Category: Transferase]]