Structural and functional identification of the uncharacterized metallo-β-lactamase superfamily protein TW9814 as a phosphodiesterase with unique metal coordination
- 주제(키워드) crystal structure , metal coordination , metallo-lactamase domains , phosphodiesterases. , TW9814 hypothetical protein , uncharacterized proteins
- 등재 SCIE, SCOPUS
- 발행기관 International Union of Crystallography
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000191210
- 본문언어 영어
- Published As https://doi.org/10.1107/S2059798322002108
- PubMed https://pubmed.ncbi.nlm.nih.gov/35362475
초록/요약
Metallo-β-lactamase (MBL) superfamily proteins have a common αβ/βα sandwich fold and perform a variety of functions through metal-mediated catalysis. However, because of the enormous scale of this superfamily, only a small percentage of the proteins belonging to the superfamily have been annotated structurally or functionally to date. Therefore, much remains unknown about the MBL superfamily proteins. Here, TW9814, a hypothetical MBL superfamily protein, was structurally and functionally investigated. Guided by the crystal structure of dimeric TW9814, it was demonstrated that TW9814 functions as a phosphodiesterase (PDE) in the presence of divalent metal ions such as manganese(II) or nickel(II). A docking model between TW9814 and the substrate bis(p-nitrophenyl)phosphate (bpNPP) showed the importance of the dimerization of TW9814 for its bpNPP-hydrolyzing activity and for the interaction between the enzyme and the substrate. TW9814 showed outstanding catalytic efficiency (k cat/K m) under alkaline conditions compared with other PDEs. The activity of TW9814 appears to be regulated through a disulfide bond, which is a feature that is not present in other MBL superfamily members. This study provides a platform for the functional characterization of other hypothetical proteins of the MBL or other superfamilies. © 2022.
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