View source for 6tty


==Structure of ClpP from Staphylococcus aureus (apo, closed state)==
<StructureSection load='6tty' size='340' side='right'caption='[[6tty]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6tty]] is a 14 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=6TTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TTY 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]] 1.9&#8491;</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=6tty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tty OCA], [https://pdbe.org/6tty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tty RCSB], [https://www.ebi.ac.uk/pdbsum/6tty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tty ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CLPP_STAA8 CLPP_STAA8] Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ADEP (acyldepsipeptide) is an exploratory antibiotic with a novel mechanism of action. ClpP, the proteolytic core of the caseinolytic protease, is deregulated towards unrestrained proteolysis. Here, we report on the mechanism of ADEP resistance in Firmicutes, as this bacterial phylum contains important pathogens to be potentially targeted by future ADEP therapy. For Staphylococcus aureus , Bacillus subtilis , enterococci and streptococci, spontaneous ADEP-resistant mutants were selected in vitro at a rate of 10 -6 . All isolates carried mutations in clpP . Characterised mutated S. aureus ClpP proteins were out-of-function and provide insight into the operation mode of ClpP. For molecular insights, crystal structures of S. aureus ClpP bound to ADEP4 were determined. Well-resolved N-terminal domains in the apo structure allow to follow the pore-gating mechanism. The collection of mutations presented here indicates residues relevant for ClpP function and suggests that ADEP-resistance will occur at a lower rate during the infection process.

Functional characterisation of ClpP mutations conferring resistance to acyldepsipeptide antibiotics in Firmicutes.,Malik IT, Pereira R, Vielberg MT, Mayer C, Straetener J, Thomy D, Famulla K, Castro H, Sass P, Groll M, Brotz-Oesterhelt H Chembiochem. 2020 Mar 17. doi: 10.1002/cbic.201900787. PMID:32181548<ref>PMID:32181548</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus]]
[[Category: Broetz-Oesterheldt H]]
[[Category: Castro HC]]
[[Category: Famulla K]]
[[Category: Groll M]]
[[Category: Malik IT]]
[[Category: Mayer C]]
[[Category: Pereira R]]
[[Category: Sass P]]
[[Category: Straetener J]]
[[Category: Thomy D]]
[[Category: Vielberg M-T]]