Browsing by Subject "Beta lactamases"
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Item Enzymology of metallo-B-lactamases(Texas Tech University, 1996-08) Glover, Bradley P.Pathogenic bacteria become resistant to penidlhns and cephalosporins through acquisition of a gene encoding the enzyme p -lactamase. (Livermore, 1991) Four classes distinguish P-lactamases as either active site serine hydrolases (class A, C and D) or zinc containmg hydrolases (class B). The class C enzyme is further distmguished from the others by being membrane bound. These bacterial enzymes catalyze the hydrolysis of the p-lactam amide group of their substrates. The class A enzyme has been studied extensively with respect to its structure, hydrolysis mechanism and inhibition. Class A enzymes proceed through an acyl-enzyme intermediate involving an active site serine residue (Fisher et al., 1980). Many substrate and transition state analogs have exhibited inhibitory effects on the class A enzyme and are used medicinally as antibiotic supplements (Wainwright, 1990). Until recently, the class B P-lactamases did not demand such study as their class A counterparts. Now, more and more clinical cases of carbapenem resistant bacteria containing the class B, zinc-requiring enzyme has caused some concern (Payne, 1993). The increased occurrence of noxious gram-positive resistant bacteria has sparked a renewed investigation into p-lactamase enzymology.Item Metal dependent beta-lactamases of Bacillus cereus(Texas Tech University, 1987-08) Price, Tracey D.The years spanning 1929-1940 were to have quite an impact on the world of medicine. A compound that displayed antibacterial properties was discovered in 1929 and named penicillin (1). Rescarch was begun in 1938 that led to the widespread use of penicillin and penicillin-related compounds as antibacterial agents in treatments of diseases (2,3). In 1940, however, the first evidence for an enzyme from bacteria that was able to catalyze the hydrolytic inactivation of penicillin was found in Escherichia coli by Abraham and Chain (4). ît was noted that bacteria which produced penicillinase and were thus resistant to penicillin had become more prevalent than sensitive strains of bacteria. Cephalosporin C, another naturalîy occurring antibacterial agent, was discovered in 1953 and was found to be more active against penicillinase-producing bacteria than natural peniciîlin (5). However, strains of bacteria resistant to this antibiotic and its related compounds have arisen and the problem of how to overcome this bacterial resistance to antibiotic treatment has beccnie increasingly important in therapeutic medicine(6).Item Production and purification of beta-lactamase II from Bacillus cereus 569/H/9(Texas Tech University, 1985-08) Thannoun, Abdulsalam Muhamed AliNot availableItem Structure-function relationships in the metallo-beta-lactamase of Bacillus cereus 5/B/6(Texas Tech University, 1995-12) Hilliard, Newton P,The major route by which pathogenic bacteria become resistant to the chemotherapeutic action of ^lactam antibiotics is through the acquisition of a gene coding for the production of enzymes called p-lactamases (P-lactamhydrolase, E.C. 3.5.2.6) (Livermore, 1991). These enzymes catalyze the hydrolytic inactivation of this type of antibiotic, thereby rendering them ineffective as antimicrobial agents (Figure 1; Livermore, 1991). A wide variety of microorganisms produce these enzymes with gram-positive bacteria producing them at highest concentrations (Citri, 1970). The p-lactamases produced by these microorganisms are divided into three classes (A, B and C) based on their physicochemical properties (Ambler, 1980; Jaurin and Gundstrom, 1981). Class A and C enzymes resemble serine proteases in their use of a catalytic serine residue and the formation of an acyl-enzyme intermediate during substrate turnover (Rahil and Pratt, 1991; Fisher et aL, 1980). Class B enzymes on the other hand are characterized by their absolute requirement for a divalent transition metal ion for catalysis (Ambler, 1980; Jaurin and Gundstrom, 1981). The native enzyme is isolated containing a catalytic zinc atom. The serine active site enzymes are sensitive to those agents which covalently modify serine residues and several inhibitors have been designed for these enzymes which make use of this and/or their catalytic mechanism (Rahil and Pratt, 1991; Gledhill et aL, 1991). The addition of clavulanic acid to the currently available p-lactam antibiotics has extended their usefulness against resistant bacterial strains (Wainwright, 1990). The metalloenzymes however have no known specific inhibitors (although a single report in the literature by Bush et aL claims inhibition of all major structural classes of the P-lactam hydrolyzing enzymes by tazobactam; the data that is contained therein show no significant level of inhibition of the class B enzymes tested (Bush et aL, 1993), other than those agents which will sequester the metal ion from the peptide or denature the peptide. The latter reagents do not offer the specificity which would be required in a pharmaceutically relevant preparation.Item The role of the metal ion in the catalytic cycle of beta-lactamase II(Texas Tech University, 1993-05) Myers, J. LynnWith beta-lactam antibiotics being the most widely used antibacterial agents in clinical use In the world today, mechanistic studies of these enzymes, called betalactamases, which are responsible for beta-lactam antibiotic resistance in pathogenic bacteria have become Increasingly Important. Mechanistic studies have enabled researchers to develop a suicide or mechanism-based inhibitor, known commercially as Augmentin, which inactivates beta-lactamase I, a class A enzyme. Currently, there are no known inhibitors of beta-lactamase II, a class B enzyme.