Identification of 2H phosphoesterase superfamily proteins with 2'-CPDase activity.

Autor: Mitsutomi S; Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan. Electronic address: shuheimitsutomi@gmail.com., Akimitsu N; Isotope Science Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan. Electronic address: akimitsu@ric.u-tokyo.ac.jp., Sekimizu K; Institute of Medical Mycology, Teikyo University, Otsuka 359, Hachiojishi, Tokyo, 192-0395, Japan. Electronic address: sekimizu@main.teikyo-u.ac.jp., Kaito C; Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Tsushima-naka 1-1-1, Kita-ku, Okayama, 700-8530, Japan. Electronic address: ckaito@okayama-u.ac.jp.
Jazyk: angličtina
Zdroj: Biochimie [Biochimie] 2019 Oct; Vol. 165, pp. 235-244. Date of Electronic Publication: 2019 Aug 15.
DOI: 10.1016/j.biochi.2019.08.008
Abstrakt: The 2H phosphoesterase superfamily (2H family) proteins are widely conserved among organisms. The 2H family is classified into several subgroups, including YjcG-like proteins whose enzymatic activity has not been reported. In the present study, we found that two YjcG-like proteins (Staphylococcus aureus SA0873 and Bacillus subtilis YjcG) have 2'-CPDase activity that hydrolyzes a 2',3'-cyclic nucleotide, thereby producing a nucleotide with a 3'-phosphate. The SA0873 protein selectively hydrolyzes a 2',3'-cyclic nucleotide with a purine base. Four SA0873 mutant proteins (H34A, T36A, H115A, and T117A), in which alanine was substituted for amino acid residues in the HxT/Sx motifs that are conserved in the 2H family, abolished the 2'-CPDase activity. Comparison of three-dimensional structures between the YjcG-like proteins with 2'-CPDase activity and another 2H family subgroup, LigT/2'-5' RNA ligase-like proteins with 3'-CPDase activity, revealed that the orientation of the substrate binding pocket is reversed between the two groups. Our findings revealed that YjcG-like proteins not only have a substrate-binding pocket different from that of LigT/2'-5' RNA ligase-like proteins, but they also have 2'-CPDase activity.
(Copyright © 2019. Published by Elsevier B.V.)
Databáze: MEDLINE
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