6o9s

<table><tr><td colspan='2'>[[6o9s]] 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=6O9S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O9S FirstGlance]. <br>

== Function ==

[https://www.uniprot.org/uniprot/MECR_STAAU MECR_STAAU] Penicillin-interactive protein and potential antirepressor.

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== Publication Abstract from PubMed ==

Methicillin-resistant Staphylococcus aureus (MRSA) infections cause significant mortality and morbidity globally. MRSA resistance to beta-lactam antibiotics is mediated by two divergons that control levels of a beta-lactamase, PC1, and a penicillin-binding protein poorly acylated by beta-lactam antibiotics, PBP2a. Expression of genes encoding these proteins is controlled by two integral membrane proteins, BlaR1 and MecR1, which both have an extracellular beta-lactam-binding sensor domain. Here, we solved the X-ray crystallographic structures of the BlaR1 and MecR1 sensor domains in complex with avibactam, a diazabicyclooctane beta-lactamase inhibitor at 1.6-2.0 A resolution. Additionally, we show that S. aureus SF8300, a clinically relevant strain from the USA300 clone of MRSA, responds to avibactam by up-regulating the expression of the blaZ and pbp2a antibiotic-resistance genes, encoding PC1 and PBP2a, respectively. The BlaR1-avibactam structure of the carbamoyl-enzyme intermediate revealed that avibactam is bound to the active-site serine in two orientations approximately 180 degrees to each other. Although a physiological role of the observed alternative pose remains to be validated, our structural results hint at the presence of a secondary sulfate-binding pocket that could be exploited in the design of future inhibitors of BlaR1/MecR1 sensor domains or the structurally similar class D beta-lactamases. The MecR1-avibactam structure adopted a singular avibactam orientation similar to one of the two states observed in the BlaR1-avibactam structure. Given avibactam up-regulates expression of blaZ and pbp2a antibiotic resistance genes, we suggest further consideration and research is needed to explore what effects administering beta-lactam-avibactam combinations have on treating MRSA infections.

Structural analysis of avibactam-mediated activation of the bla and mec divergons in methicillin-resistant Staphylococcus aureus.,Alexander JAN, Radaeva M, King DT, Chambers HF, Cherkasov A, Chatterjee SS, Strynadka NCJ J Biol Chem. 2020 Aug 7;295(32):10870-10884. doi: 10.1074/jbc.RA120.013029. Epub , 2020 Jun 9. PMID:32518158<ref>PMID:32518158</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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== References ==

<references/>

[[Category: Staphylococcus aureus]]