Structural highlights
Function
[A0A1I7CHQ2_9GAMM] Splits dipeptides with a prolyl residue in the C-terminal position.[HAMAP-Rule:MF_01279][SAAS:SAAS01095084]
Publication Abstract from PubMed
Enzyme promiscuity is critical to the acquisition of evolutionary plasticity in cells and can be recruited for high-value chemical synthesis or xenobiotic degradation. The molecular determinants of substrate ambiguity are essential to this activity; however, these details remain unknown. Here, we performed the directed evolution of a prolidase to enhance its initially weak paraoxonase activity. The in vitro evolution led to an unexpected 1,000,000-fold switch in substrate selectivity, with a 30-fold increase in paraoxon hydrolysis and 40,000-fold decrease in peptide hydrolysis. Structural and in silico analyses revealed enlarged catalytic cavities and substrate repositioning as responsible for rapid catalytic transitions between distinct chemical reactions.
Repurposing a bacterial prolidase for organophosphorus hydrolysis: Reshaped catalytic cavity switches substrate selectivity.,Yang J, Xiao YZ, Li R, Liu Y, Long LJ Biotechnol Bioeng. 2020 Sep;117(9):2694-2702. doi: 10.1002/bit.27455. Epub 2020, Jun 26. PMID:32515491[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yang J, Xiao YZ, Li R, Liu Y, Long LJ. Repurposing a bacterial prolidase for organophosphorus hydrolysis: Reshaped catalytic cavity switches substrate selectivity. Biotechnol Bioeng. 2020 Sep;117(9):2694-2702. doi: 10.1002/bit.27455. Epub 2020, Jun 26. PMID:32515491 doi:http://dx.doi.org/10.1002/bit.27455
