Structure-function relationships of the 5-oxoprolinase subunit A: Guiding biological sciences students down the path less traveled.

Autor: Oke M; Department of Biological Sciences, Fountain University, Osogbo, Nigeria., Oni O; Department of Chemical Sciences, Fountain University, Osogbo, Nigeria., Bello R; Department of Chemical Sciences, Fountain University, Osogbo, Nigeria., Samuel-Omoyajowo K; Department of Biological Sciences, Fountain University, Osogbo, Nigeria., Senbadejo T; Department of Biological Sciences, Fountain University, Osogbo, Nigeria.
Jazyk: angličtina
Zdroj: Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology [Biochem Mol Biol Educ] 2019 Nov; Vol. 47 (6), pp. 620-631. Date of Electronic Publication: 2019 Sep 14.
DOI: 10.1002/bmb.21300
Abstrakt: Bioinformatics was recently introduced as a module for both undergraduate and postgraduate biological sciences students at our institution. Our experience shows that inquiry-based hands-on exercises provide the most efficient approach to bioinformatic straining. In this article, we report a structural bioinformatics project carried out by Master degree students to determine structure-function relationships of the uncharacterized prokaryotic 5-oxoprolinase subunit A (PxpA). PxpA associates with the PxpBC complex to form a functional 5-oxoprolinase enzyme for conversion of 5-oxoproline to L-glutamate. Although the exact role of PxpA is yet to be determined, it has been demonstrated that PxpBC catalyses the first step of the reaction, which is phosphorylation of 5-oxoproline. Here, we provide evidence that PxpA is involved in the last two steps of the reaction:decyclization of the labile phosphorylated 5-oxoproline to the equally labile γ-glutamylphosphate, and subsequent dephosphorylation to L-glutamate. Structural bioinformatics analysis of four putative PxpA structures revealed that PxpA adopts a non-canonical TIM barrel fold with well-characterized TIM barrel enzyme features. These include a C-terminal groove comprising potentially essential conserved amino acid residues organized into putative motifs. Phylogenetic analysis suggests a relationship between taxonomic grouping and PxpA oligomerization. PxpA forms a tunnel upon ligand binding, thus suggesting that the PxpABC complex employs the mechanism of substrate channeling to protect labile intermediates. Ultimately, students were able to form a testable hypothesis on the function of PxpA, an achievement we consider encouraging other students to emulate. © 2019 International Union of Biochemistry and Molecular Biology, 47(6):620-631, 2019.
(© 2019 International Union of Biochemistry and Molecular Biology.)
Databáze: MEDLINE
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