Shaibullah, Sofiyah and Shuhaimi, Nurshahirah and Ker, De-Sheng and Mohd-Sharif, Nurhikmah and Ho, Kok Lian and Teh, Aik-Hong and Waterman, Jitka and Tang, Thean-Hock and Wong, Rui-Rui and Nathan, Sheila and Mohamed, Rahmah and Ng, Min Jia and Fung, Shin-Yee and Jonet, Mohd Anuar and Firdaus-Raih, Mohd and Ng, Chyan Leong (2023) Structural and functional analyses of Burkholderia pseudomallei BPSL1038 reveal a Cas-2/VapD nuclease sub-family. Communications Biology, 6 (1). ISSN 2399-3642, DOI https://doi.org/10.1038/s42003-023-05265-4.
Full text not available from this repository.Abstract
Burkholderia pseudomallei is a highly versatile pathogen with similar to 25% of its genome annotated to encode hypothetical proteins. One such hypothetical protein, BPSL1038, is conserved across seven bacterial genera and 654 Burkholderia spp. Here, we present a 1.55 angstrom resolution crystal structure of BPSL1038. The overall structure folded into a modified beta alpha beta beta alpha beta alpha ferredoxin fold similar to known Cas2 nucleases. The Cas2 equivalent catalytic aspartate (D11) pairs are conserved in BPSL1038 although B. pseudomallei has no known CRISPR associated system. Functional analysis revealed that BPSL1038 is a nuclease with endonuclease activity towards double-stranded DNA. The DNase activity is divalent ion independent and optimum at pH 6. The concentration of monovalent ions (Na+ and K+) is crucial for nuclease activity. An active site with a unique D-11(X20)SST motif was identified and proposed for BPSL1038 and its orthologs. Structure modelling indicates the catalytic role of the D-11(X20)SST motif and that the arginine residues R10 and R30 may interact with the nucleic acid backbone. The structural similarity of BPSL1038 to Cas2 proteins suggests that BPSL1038 may represent a sub-family of nucleases that share a common ancestor with Cas2.
| Item Type: | Article |
|---|---|
| Funders: | Universiti Kebangsaan Malaysia (GUP-2017-070) ; (DIP-2012-13) ; (GGPM-2012-069), Ministry of Education, Malaysia (ERGS/1/2011/STG/UKM/01/15) |
| Subjects: | R Medicine > R Medicine (General) |
| Divisions: | Faculty of Medicine > Department of Molecular Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 08 Sep 2025 01:16 |
| Last Modified: | 08 Sep 2025 01:16 |
| URI: | http://eprints.um.edu.my/id/eprint/50651 |
Actions (login required)
 |
View Item |
