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Substrate specificity of HMRZ-86 for beta-lactamases, including extended-spectrum beta-lactamases (ESBLs). 2007

Hideaki Hanaki, and Yuuji Koide, and Hiroaki Yamazaki, and Ryoichi Kubo, and Tomota Nakano, and Koichiro Atsuda, and Keisuke Sunakawa
Research Center for Anti-Infective Drugs, Kitasato Institute, Minato-ku, Tokyo, Japan.

HMRZ-86 was designed as a new chromogenic cephalosporin to detect extended-spectrum beta-lactamases (ESBLs) and similar evolved beta-lactamases, such as metallo-beta-lactamases, derepressed AmpC, and extended oxacillinase. We report here our investigation of the kinetic parameters of several types of beta-lactamases to show the enzymatic characteristics of HMRZ-86. The Michaelis constant (Km values of HMRZ-86 for ESBLs were twice to three and half times as high as those of nitrocefin, and the maximum velocity (Vmax) was one-fifth that of nitrocefin. The Km and Vmax of HMRZ-86 for AmpC were both smaller than those of nitrocefin. The kinetic parameters of HMRZ-86 for metallo beta-lactamase (MBL) were very variable, depending on the type of buffer solution used and the concentration of zinc ions. For MBL, the Km values of HMRZ-86 were higher than those of nitrocefin, but the Vmax values were almost the same as those of nitrocefin. Although the chemical structure of HMRZ-86 is similar to that of nitrocefin, we think the enzymatic reactivities of the two entities for beta-lactamases are very different.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D002511 Cephalosporins A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus ACREMONIUM. They contain the beta-lactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. Antibiotics, Cephalosporin,Cephalosporanic Acid,Cephalosporin,Cephalosporin Antibiotic,Cephalosporanic Acids,Acid, Cephalosporanic,Acids, Cephalosporanic,Antibiotic, Cephalosporin,Cephalosporin Antibiotics
D006090 Gram-Negative Bacteria Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. Gram Negative Bacteria
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001618 beta-Lactamases Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. beta-Lactamase,beta Lactamase,beta Lactamases
D013379 Substrate Specificity A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. Specificities, Substrate,Specificity, Substrate,Substrate Specificities

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