| Structural highlights
Function
BLO23_ACIBA Class D beta-lactamase which confers resistance to the beta-lactam antibiotics, including ampicillin, and carbapenems such as imipenem and meropenem (PubMed:18725452, PubMed:20194701, PubMed:24012371, PubMed:30530607, PubMed:35420470). Acts via hydrolysis of the beta-lactam ring (PubMed:23877677, PubMed:24012371, PubMed:30530607, PubMed:35420470). Has penicillin-, cephalosporin- and carbapenem-hydrolyzing activities, but lacks ceftazidime-hydrolyzing activity (PubMed:23877677, PubMed:24012371, PubMed:30530607, PubMed:35420470).[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Dissemination of Acinetobacter baumannii strains harboring class D beta-lactamases producing resistance to carbapenem antibiotics severely limits our ability to treat deadly Acinetobacter infections. Susceptibility determination in the A. baumannii background and kinetic studies with a homogeneous preparation of OXA-23 beta-lactamase, the major carbapenemase present in A. baumannii, document the ability of this enzyme to manifest resistance to last-resort carbapenem antibiotics. We also report three X-ray structures of OXA-23: apo OXA-23 at two different pH values, and wild-type OXA-23 in complex with meropenem, a carbapenem substrate. The structures and dynamics simulations reveal an important role for Leu166, whose motion regulates the access of a hydrolytic water molecule to the acyl-enzyme species in imparting carbapenemase activity.
Structural Basis for Carbapenemase Activity of the OXA-23 beta-Lactamase from Acinetobacter baumannii.,Smith CA, Antunes NT, Stewart NK, Toth M, Kumarasiri M, Chang M, Mobashery S, Vakulenko SB Chem Biol. 2013 Sep 19;20(9):1107-15. doi: 10.1016/j.chembiol.2013.07.015. Epub, 2013 Sep 5. PMID:24012371[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Adams-Haduch JM, Paterson DL, Sidjabat HE, Pasculle AW, Potoski BA, Muto CA, Harrison LH, Doi Y. Genetic basis of multidrug resistance in Acinetobacter baumannii clinical isolates at a tertiary medical center in Pennsylvania. Antimicrob Agents Chemother. 2008 Nov;52(11):3837-43. PMID:18725452 doi:10.1128/AAC.00570-08
- ↑ Lin YC, Hsia KC, Chen YC, Sheng WH, Chang SC, Liao MH, Li SY. Genetic basis of multidrug resistance in Acinetobacter clinical isolates in Taiwan. Antimicrob Agents Chemother. 2010 May;54(5):2078-84. PMID:20194701 doi:10.1128/AAC.01398-09
- ↑ Kaitany KC, Klinger NV, June CM, Ramey ME, Bonomo RA, Powers RA, Leonard DA. STRUCTURES OF THE CLASS D CARBAPENEMASES OXA-23 AND OXA-146: MECHANISTIC BASIS OF ACTIVITY AGAINST CARBAPENEMS, EXTENDED-SPECTRUM CEPHALOSPORINS AND AZTREONAM. Antimicrob Agents Chemother. 2013 Jul 22. PMID:23877677 doi:10.1128/AAC.00762-13
- ↑ Smith CA, Antunes NT, Stewart NK, Toth M, Kumarasiri M, Chang M, Mobashery S, Vakulenko SB. Structural Basis for Carbapenemase Activity of the OXA-23 beta-Lactamase from Acinetobacter baumannii. Chem Biol. 2013 Sep 19;20(9):1107-15. doi: 10.1016/j.chembiol.2013.07.015. Epub, 2013 Sep 5. PMID:24012371 doi:10.1016/j.chembiol.2013.07.015
- ↑ Stewart NK, Smith CA, Antunes NT, Toth M, Vakulenko SB. Role of the Hydrophobic Bridge in the Carbapenemase Activity of Class D beta-Lactamases. Antimicrob Agents Chemother. 2018 Dec 10. pii: AAC.02191-18. doi:, 10.1128/AAC.02191-18. PMID:30530607 doi:http://dx.doi.org/10.1128/AAC.02191-18
- ↑ Stewart NK, Toth M, Alqurafi MA, Chai W, Nguyen TQ, Quan P, Lee M, Buynak JD, Smith CA, Vakulenko SB. C6 Hydroxymethyl-Substituted Carbapenem MA-1-206 Inhibits the Major Acinetobacter baumannii Carbapenemase OXA-23 by Impeding Deacylation. mBio. 2022 Apr 14:e0036722. doi: 10.1128/mbio.00367-22. PMID:35420470 doi:http://dx.doi.org/10.1128/mbio.00367-22
- ↑ Smith CA, Antunes NT, Stewart NK, Toth M, Kumarasiri M, Chang M, Mobashery S, Vakulenko SB. Structural Basis for Carbapenemase Activity of the OXA-23 beta-Lactamase from Acinetobacter baumannii. Chem Biol. 2013 Sep 19;20(9):1107-15. doi: 10.1016/j.chembiol.2013.07.015. Epub, 2013 Sep 5. PMID:24012371 doi:10.1016/j.chembiol.2013.07.015
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