6-AmpC

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. 

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. 

Powers RA, Morandi F, Shoichet BK. Structure-based discovery of a novel, noncovalent inhibitor of AmpC beta-lactamase. Structure 2002 10 1013-23. 

Fig. 2.33. H2Saq concentration.s as a function of temperature for hot spring fluids at midocean ridges as a function of redox. Assuming AMPC (anhydrite-magnetite-pyrite-calcite) and PPM (pyrite-pyrrhotite) buffers redox in sub-seafloor reaction zones and a pressure of 500 bars, dissolved H2Saq concentrations indicate temperatures of approximately 370-385°C. Solid star Okinawa. (Modified after Seyfried and Ding, 1995.)...

Macrophages Galactose (particles), mannose-fucose, acetylated LDL, alpha2-macroglobulin-Protease complex (AMPC)... 

Fibroblasts Transferrin, epidermal growth factor, LDL, mannose-6-phosphate, transcobalamine II, AMPC, mannose... 

Keywords AmpC /3-Lactamase /3-Lactam Cephem Inhibitor Metalloenzyme ... 

In comparison to sulbactam, penam sulfones 12a and b exhibited excellent activity against TEM-1 and AmpC enzymes, respectively, with over 2500-fold improvement against the class C enzyme. Within the same series, 12a and 12b are appreciably more potent than their corresponding diastereomers. In particular, they are potent against the AmpC enzyme suggesting the stereochemical preference of the alkoxy substituent of the cyclopropyl ring, which plays a critical role in binding with the enzymes. Further, in vitro evaluations in a cell-based assay (MIC) established the effectiveness of 12a. hi... 

Further, using a combination of X-ray crystallography and mass spectroscopy, Knox et al. [73] has firmly established a central role for Ser-130 in the inhibition of SHV-1 /1-lactamase (class A) by tazobactam. Many additional modifications (Table 3) were carried out on tazobactam with the aim of increasing inhibitory activity against AmpC enzymes, but none of these derivatives (e.g., 13c, 13d, and 13e) had any advantage over tazobactam [74— 77]. Renewed interest in the modification at the C-2 position of sulbactam was developed when scientists from Hoffmann-La Roche disclosed a series of 2/J-alkenyl penam sulfones that possess the ability to simultaneously inactivate both class A penicillinase as well as class C cephalosporinase. Compound... 

FP 1380 AmpC (3-lactamase over-producing clinical isolate... 

PAOl A AmpD/PAOl AmpD-deleted AmpC (3-lactamase over expression strain... 

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. 

Engineering Design Handbook, Principles of Explosive Behavior, AMPC 706-180, US Army Material Command, Washington, DC, 1972. 

Hsieh, J. H., Wang, X. S., Teotico, D., Golbraikh, A., Tropsha, A. (2008) Differentiation of AmpC beta-lactamase binders vs. decoys using classification kNN QSAR modeling and application of the QSAR classifier to virtual screening. J Comput Aided Mol Des 22, 593-609. 

PATR 1740, reissued by US Army Materiel Command, Washington, DC, 20315 as Pamphlet AMPC 706-177 (1967), pp 122—27 (Military Dynamites) 66) Anon, "Military Explosives ,... 

KC Usher, LC Blaszczak, GS Weston, BK Shoichet, SJ Remington. Three-dimensional structure of AmpC (3-lactamase from Escherichia coli bound to a transition-state analogue possible implications for the oxyanion hypothesis and for inhibitor design. Biochemistry 37 16082-16092, 1998. 

GS Weston, J Blazquez, F Baquero, BK Shoichet. Structure-based enhancement of boronic acid-based inhibitors of AmpC (3-lactamase. JMedCheni41 4577 4586,1998. 

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