7tbx

<table><tr><td colspan='2'>[[7tbx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TBX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TBX FirstGlance]. <br>

== Function ==

[https://www.uniprot.org/uniprot/BLKPC_KLEPN BLKPC_KLEPN] Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency.

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

Klebsiella pneumoniae carbapenemases (KPC-2 and KPC-3) present a global clinical threat, as these beta-lactamases confer resistance to carbapenems and oxyimino-cephalosporins. Recent clinically identified KPC variants with substitutions at Ambler position D179, located in the Omega loop, are resistant to the beta-lactam/beta-lactamase inhibitor combination ceftazidime-avibactam, but susceptible to meropenem-vaborbactam. To gain insights into ceftazidime-avibactam resistance conferred by D179N/Y variants of KPC-2, crystal structures of these variants were determined. The D179N KPC-2 structure revealed that the change of the carboxyl to an amide moiety at position 179 disrupted the salt bridge with R164 present in wild-type KPC-2. Additional interactions were disrupted in the Omega loop, causing a decrease in the melting temperature. Shifts originating from N179 were also transmitted toward the active site, including approximately 1-A shifts of the deacylation water and interacting residue N170. The structure of the D179Y KPC-2 beta-lactamase revealed more drastic changes, as this variant exhibited disorder of the Omega loop, with other flanking regions also being disordered. We postulate that the KPC-2 variants can accommodate ceftazidime because the Omega loop is displaced in D179Y or can be more readily displaced in D179N KPC-2. To understand why the beta-lactamase inhibitor vaborbactam is less affected by the D179 variants than avibactam, we determined the crystal structure of D179N KPC-2 in complex with vaborbactam, which revealed wild-type KPC-2-like vaborbactam-active site interactions. Overall, the structural results regarding KPC-2 D179 variants revealed various degrees of destabilization of the Omega loop that contribute to ceftazidime-avibactam resistance, possible substrate-assisted catalysis of ceftazidime, and meropenem and meropenem-vaborbactam susceptibility.

Structural Characterization of the D179N and D179Y Variants of KPC-2 beta-Lactamase: Omega-Loop Destabilization as a Mechanism of Resistance to Ceftazidime-Avibactam.,Alsenani TA, Viviani SL, Kumar V, Taracila MA, Bethel CR, Barnes MD, Papp-Wallace KM, Shields RK, Nguyen MH, Clancy CJ, Bonomo RA, van den Akker F Antimicrob Agents Chemother. 2022 Mar 28:e0241421. doi: 10.1128/aac.02414-21. PMID:35341315<ref>PMID:35341315</ref>

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

</div>

<div class="pdbe-citations 7tbx" style="background-color:#fffaf0;"></div>

[[Category: Klebsiella pneumoniae]]