AmpC P-lactamase

AmpC P-Lactamase Phosphodiesterase 4 Protein Tyrosine Phosphatase IB... 

AmpC P-Lactamase. A map of hot spots was constructed from the X-ray structure of AmpC P-lactamase and a university version of the program DOCK was used to search for noncovalent inhibitors in 229,810 compounds of the ACD database. Of 56 tested compounds three had values <650pM, for example, compound 41 Ki = 26pM Fig. 16.6) [117]. The experimental X-ray structure of its complex with AmpC P-lactamase closely resembles the predicted binding mode. 

AmpC 3-lactamase A competitive, non-covalent inhibitor of AmpC p-lactamase was identified by virtual 148... 

Powers, R. A., Morandi, R, Shoichet, B. K. Structure-based discovery of a novel, noncovalent inhibitor of AmpC P-lactamase. Structure, 2002,10, 1013-1023. 

Cephalosporinases 2a C AmpC p-lactamases hydrolysis of all P-lactams, except of carbapenems (and mostly fourth generation cephalosporins) non-inhib-ited by conventional serine inhibitors (i.e., elavulanic acid, tazobactam, and sulbactam)... 

The MALDI-TOF MS assay described above was able to detect the presence of an approximately 39,850-w/z peak, which can be used as an indicator for the presence of the C. ew c(//-derived CMY-2-like group of the acquired AmpC P-lactamases (Papagiannitsis et al. 2014). In addition, the observation of the 39,670 and 38,900-w/z peaks for ACC-4 and DHA-1 enzymes, respectively, indicated that MALDI-TOF MS may discriminate the diverse groups of acquired AmpC-type cephalosporinases (see Fig. 12.4). In addition, the latter method revealed a peak at mIz 383, representing the putative acyl-enzyme complex (complex of CMY-2 P-lactamase with the meropenem molecule). 

These recent data indicate that MALDI-TOF MS has the potential to directly detect the most clinically important AmpC P-lactamases, such as the CMY-2-like, ACC, and DHA types, in clinical isolates of Enterobacteriaceae. In agreement with other MALDI-TOF MS applications (Hrabak 2013), the described protocol is quick and economical. In addition, detection of p-lactamases by MALDI-TOF MS in a proteomic approach allowing the study of the behavior of the tested strains can complement the already used techniques for characterization of P-lactamases, such as PCR and isoelectric focusing (lEF). MALDI-TOF MS can directly detect the class A (Camara and Hays 2007) and class C p-lactamases, as well as other mechanisms such as methylation of rRNA and cell wall components (Cai et al. 2012 Hrabak et al. 2013). We conclude that establishing a MALDI-TOF supplementary database of resistance mechanisms would promote further research in this field. 

Benzo[b]thiophene-2-boronic acid AmpC P-lactamase 27 107,108... 

Class C Serine p-lactamases AmpC enzymes of coti, Shigella spp., Enterobacterspp., C. freundii, M. morganii, Providencia spp. and Serratia spp. cephalos-porinases with wide spectrum of activity CMY, LAT, BIL, MOX, ACC, FOX and DHA types. All genes are ampC genes that have been mobilized by transfer to plasmid DNA. 

A. Dubus, S. Normarj, M. Kania, M. G. P. Page, The Role of Tyrosine 150 in Catalysis of /3-Lactam Hydrolysis by AmpC /3-Lactamase from Escherichia coli Investigated by Site-Directed Mutagenesis , Biochemistry 1994, 33, 8577-8586. 

Continuing use of the third-generation cephalosporins and the introduction of p-lactamase inhibitor combinations (clavulanate with amoxycillin or ticarcillin, sulbactam with ampicillin, and tazobactam with piperacillin see section 4.2) resulted in the appearance of plasmids encoding class C P-lactamases. After several unconfirmed reports, the first proof that a class C P-lactamase had been captured on a plasmid came in 1990 when transmissible resistance to a-methoxy and oxyimino-P-lactams was shown to be mediated by an enzyme whose gene was 90% identical to the ampC gene of E. cloacae. They have subsequently been found worldwide. Strains with plasmid-mediated AmpC enzymes are typically resistant to aminopenicillins (ampicillin or amoxycillin), carboxypenicillins (carbenicillin or ticarcillin) and ureidopenicillins (piperacillin). The enzymes also provide resistance to the oxyimino cephalosporins (ceftazidime, cefo-... 

Cephalosporins Extended spectrum P-lactamases chromosomal P-lactamases (AmpC) plasmid P-lactamases (TEM-1, SHV-1)... 

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