Export bibliographic data
Literature by the same author
plus on the publication server
plus at Google Scholar


Molecular engineering of organophosphate hydrolysis activity from a weak promiscuous lactonase template

Title data

Meier, Monika M. ; Rajendran, Chitra ; Malisi, Christoph ; Fox, Nicholas G. ; Xu, Chengfu ; Schlee, Sandra ; Barondeau, David P. ; Höcker, Birte ; Sterner, Reinhard ; Raushel, Frank M.:
Molecular engineering of organophosphate hydrolysis activity from a weak promiscuous lactonase template.
In: Journal of the American Chemical Society. Vol. 135 (7 August 2013) Issue 31 . - pp. 11670-11677.
ISSN 1520-5126
DOI: https://doi.org/10.1021/ja405911h

Project information

Project title:
Project's official titleProject's id
NIH GrantGM 68550

Project financing: National Institutes of Health

Abstract in another language

Rapid evolution of enzymes provides unique molecular insights into the remarkable adaptability of proteins and helps to elucidate the relationship between amino acid sequence, structure, and function. We interrogated the evolution of the phosphotriesterase from Pseudomonas diminuta (PdPTE), which hydrolyzes synthetic organophosphates with remarkable catalytic efficiency. PTE is thought to be an evolutionarily "young" enzyme, and it has been postulated that it has evolved from members of the phosphotriesterase-like lactonase (PLL) family that show promiscuous organophosphate-degrading activity. Starting from a weakly promiscuous PLL scaffold (Dr0930 from Deinococcus radiodurans ), we designed an extremely efficient organophosphate hydrolase (OPH) with broad substrate specificity using rational and random mutagenesis in combination with in vitro activity screening. The OPH activity for seven organophosphate substrates was simultaneously enhanced by up to 5 orders of magnitude, achieving absolute values of catalytic efficiencies up to 10(6) M(-1) s(-1). Structural and computational analyses identified the molecular basis for the enhanced OPH activity of the engineered PLL variants and demonstrated that OPH catalysis in PdPTE and the engineered PLL differ significantly in the mode of substrate binding.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry > Chair Biochemistry - Univ.-Prof. Dr. Birte Höcker
Result of work at the UBT: No
DDC Subjects: 500 Science > 500 Natural sciences
500 Science > 540 Chemistry
500 Science > 570 Life sciences, biology
Date Deposited: 27 Jan 2021 07:22
Last Modified: 27 Jan 2021 07:22
URI: https://eref.uni-bayreuth.de/id/eprint/62432