Dependence of Hydrolysis of .BETA.-Lactams with a Zinc(II)-.BETA.-Lactamase Produced from Serratia marcescens (IMP-1) on pH and Concentration of Zinc(II) Ion: Dissociation of Zn(II) from IMP-1 in Acidic Medium

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  • Goto Masafumi
    Laboratory of Pharmaceutical Physical Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University
  • Yasuzawa Hisami
    Laboratory of Pharmaceutical Physical Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University
  • Higashi Toshihiro
    Laboratory of Pharmaceutical Physical Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University
  • Yamaguchi Yoshihiro
    Laboratory of Pharmaceutical Physical Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University
  • Kawanami Akiko
    Laboratory of Pharmaceutical Physical Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University
  • Mifune Shiho
    Laboratory of Pharmaceutical Physical Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University
  • Mori Hiromasa
    Laboratory of Pharmaceutical Physical Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University
  • Nakayama Hitoshi
    Laboratory of Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University
  • Harada Kumiko
    Laboratory of Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University
  • Arakawa Yoshichika
    Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Japan

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  • Dependence of Hydrolysis of β-Lactams with a Zinc(II)-β-Lactamase Produced from Serratia marcescens (IMP-1) on pH and Concentration of Zinc(II) Ion: Dissociation of Zn(II) from IMP-1 in Acidic Medium
  • Dependence of Hydrolysis of ベータ Lactams with a Zinc 2 ベータ Lactamase Produced from Serratia marcescens IMP 1 on pH and Concentration of Zinc 2 Ion Dissociation of Zn 2 from IMP 1 in Acidic Medium

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The pH dependence for the hydrolysis of β-lactam antibiotics by a metallo-β-lactamase (IMP-1) produced from Serratia marcescens was investigated varying the concentration of Zn(II). The activity of IMP-1 for imipenem was decreased at pH less than pH 5.3 without external addition of Zn(II) ions but was recovered with addition of Zn(II). Varying the concentration of external Zn(II), the molar activity of the enzyme, kobs, that was defined by the velocity of hydrolysis of imipenem/concentration of IMP-1 was expressed by kobs=vinit/[E]T=kmax[Zn]/(Kd+[Zn]) in which Kd stands for the dissociation constant between Zn(II) and IMP-1. The dissociation constants, Kd, vary with pH; Kd=840×10−6 M at pH 4.3 and Kd=0.19×10−6 M at pH 6.0. The plot of −log Kd against pH showed a straight line having a slope of 4.0 below pH 5.0, showing the existence of four functional groups which may be protonated upon dissociation of Zn(II) ion(s). The kcat, Km, and kcat/Km of hydrolysis of imipenem and cephalothin in the presence of sufficient concentration of Zn(NO3)2 for saturation of IMP-1 with Zn(II) showed similar dependency to each other on pH between pH 6.0 and 9.0.

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