Biochemistry (Moscow)

, Volume 75, Issue 3, pp 336–341 | Cite as

Studies on amino acid replacement and inhibitory activity of a β-lactamase inhibitory peptide

  • Liping Xie
  • Mingfei Xu
  • Tao Yang
  • Chunbao Zhu
  • Baoquan Zhu
  • Youjia HuEmail author


An SHV β-lactamase gene was amplified from a β-lactam resistant Klebsiella pneumoniae K-71 genomic DNA. After expression and purification, we demonstrated that peptide P1 could inhibit the hydrolysis activity of both TEM-1 and SHV β-lactamase in vitro. Three mutations were introduced into P1 in which the first residue S was replaced by F, the 18th residue V was mutated to Y, and the 15th residue Y was substituted with A, C, G, and R to obtain the mutants of P1-A, P1- C, P1-G, and P1-R, respectively. The mutant peptides were purified and their inhibitory constants against TEM-1 and SHV β-lactamase were determined. All these β-lactamase inhibitory peptides could inhibit the activity of both β-lactamases, while the mutant peptides showed stronger inhibitory activities against TEM-1 β-lactamase than against SHV β-lactamase. Inhibition data suggested that P1-A improved the β-lactamase inhibitory activity by over 3-fold compare to P1. When P1-A was incubated with K. pneumoniae K-71 in Luria-Bertani medium containing ampicillin, it showed a much stronger growth of inhibition ratio over P1. This study gives us a good candidate for development of novel β-lactamase inhibitors.

Key words

β-lactamase inhibitory peptide β-lactamase amino acid replacement Klebsiella pneumoniae inhibitory constant 



β-lactamase inhibitory peptide




minimal inhibitory concentration


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Copyright information

© Pleiades Publishing, Ltd. 2010

Authors and Affiliations

  • Liping Xie
    • 1
  • Mingfei Xu
    • 1
  • Tao Yang
    • 1
  • Chunbao Zhu
    • 1
  • Baoquan Zhu
    • 1
  • Youjia Hu
    • 1
    Email author
  1. 1.State Key Laboratory of New Drug and Pharmaceutical ProcessShanghai Institute of Pharmaceutical IndustryShanghaiChina

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