Functional and structural analysis of trehalose-6-phosphate phosphatase from Burkholderia pseudomallei: Insights into the catalytic mechanism
Articolo
Data di Pubblicazione:
2020
Citazione:
Functional and structural analysis of trehalose-6-phosphate phosphatase from Burkholderia pseudomallei: Insights into the catalytic mechanism / S. Suthisawat, L.J. Gourlay, M. Bolognesi, U. Boonyuen, M. Vanaporn. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - 523:4(2020), pp. 979-984.
Abstract:
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Burkholderia pseudomallei; Catalysis; Enzyme crystal structure; Trehalose-6-phosphate phosphatase
Elenco autori:
S. Suthisawat, L.J. Gourlay, M. Bolognesi, U. Boonyuen, M. Vanaporn
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