Journal
JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 184, Issue -, Pages 8-14Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2018.04.008
Keywords
Enzyme evolution; Metallo-hydrolase; Phosphotriesterase; Reaction mechanism; Density functional theory
Funding
- National Natural Science Foundation of China [21203042, 11574062, 21503083, 21673025]
- Natural Science Foundation of Gansu Province [145RJYA285]
- Fundamental Research Funds for the Central Universities [31920150027]
- Open Project of Key Laboratory of Polyoxometalate Science of Ministry of Education (NENU)
- State Key Laboratory of Supramolecular Structure and Materials (JLU) [SKLSSM201723]
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Metallo-beta-lactamase (M beta L) is a eubacterial zinc metallo-hydrolase superfamily. Despite their well-known lactamase activities, M beta L family members also have the ability to catalyze phosphotriester hydrolysis with different phosphotriesterase activities. In the present study, based on crystal structure comparisons of the related MIlL members, a series of models was constructed and calculated using the density functional theory (DFT) method to explore the relationship between active-site changes and phosphotriesterase activities. These calculations show that the energetic barriers for phosphotriesterase activity are considerably reduced due to active-site differences, which describes an evolutionary trend for the development of phosphotriesterase activity in the M beta L super-family. The key event is the appearance of a specialized and negatively charged residue bridging both zinc ions, which plays the two important roles of maintaining charge balance and stabilizing the binuclear active-site structure. This pathway is also consistent with the evolutionary relationships determined by phylogenetic tree analysis using complete residue sequences. Our studies provide the first methodology to explore the development of a new enzyme activity within a superfamily, and to shed new light on understanding the catalytic mechanism from an evolutionary perspective.
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