Publication: Functional and structural analysis of trehalose-6-phosphate phosphatase from Burkholderia pseudomallei: Insights into the catalytic mechanism
Issued Date
2020-03-19
Resource Type
ISSN
10902104
0006291X
0006291X
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2-s2.0-85078070953
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Mahidol University
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SCOPUS
Bibliographic Citation
Biochemical and Biophysical Research Communications. Vol.523, No.4 (2020), 979-984
Suggested Citation
Sarocha Suthisawat, Louise Jane Gourlay, Martino Bolognesi, Usa Boonyuen, Muthita Vanaporn Functional and structural analysis of trehalose-6-phosphate phosphatase from Burkholderia pseudomallei: Insights into the catalytic mechanism. Biochemical and Biophysical Research Communications. Vol.523, No.4 (2020), 979-984. doi:10.1016/j.bbrc.2019.12.088 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/53564
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Title
Functional and structural analysis of trehalose-6-phosphate phosphatase from Burkholderia pseudomallei: Insights into the catalytic mechanism
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Abstract
© 2020 Elsevier Inc. We report the functional and structural characterization of trehalose-6-phosphate phosphatase (TPP), from the Gram-negative bacterium B. pseudomallei that causes melioidosis, a severe infectious disease endemic in Southeast Asia and Northern Australia. TPP is a key enzyme in the trehalose biosynthesis pathway, which plays an important role in bacterial stress responses. Due to the absence of this biosynthetic pathway in mammals, TPP has drawn attention as a potential drug target, to combat antibiotic resistance. In this context, we present a detailed biochemical analysis of purified recombinant TPP, reporting its specific high catalytic activity toward the trehalose-6-phosphate substrate, and an absolute requirement for its Mg2+ cofactor. Furthermore, we present the crystal structure of TPP solved at 1.74 Å, revealing the canonical haloacid dehalogenase (HAD) superfamily fold and conserved substrate binding pocket, from which insights into the catalytic mechanism may be deduced. Our data represent a starting point for the rational design of antibacterial drugs.