Substrate specificity of HMRZ-86 for beta-lactamases, including extended-spectrum beta-lactamases (ESBLs).
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.
Hanaki
Hideaki
H
Research Center for Anti-Infective Drugs, Kitasato Institute, Minato-ku, Tokyo, Japan.
Koide
Yuuji
Y
Yamazaki
Hiroaki
H
Kubo
Ryoichi
R
Nakano
Tomota
T
Atsuda
Koichiro
K
Sunakawa
Keisuke
K
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D002511:Cephalosporins / Q000737:chemistry / Q000378:metabolism*; D006090:Gram-Negative Bacteria / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D013379:Substrate Specificity; D001618:beta-Lactamases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C487639:HMRZ 86; D001618:beta-Lactamases; C021720:nitrocefin