Moe Team || DNA repair

Our main research activity is within the field of DNA repair, with a strong focus on Base Excision Repair (BER). In order to provide new information to this field we use an integrated structural biology approach and study BER enzymes from a wide range of organisms including the extremely radiation and desiccation resistant bacterium Deinococcus radiodurans, the fish pathogen Aliivibrio salmonicida, the human pathogen Vibrio cholerae, Atlantic cod (Gadus morhua) and human. The majority of our enzymes originate from D. radiodurans, which tolerates 200 times higher radiation doses than other microorganisms, without losing viability. The mechanism behind the high radiation resistance is not known but is probably a result of the dual resistance (radiation and desiccation) and a combination of a highly efficient DNA repair machinery, a densely packed genome and cell wall and an unusual high intracellular concentration of Manganese. The genome possesses an unusual high number of BER enzymes compared to other microorganisms, which indicates that BER is important for the resistance mechanism of this organism. We also have some research activity related to iron metabolism in bacteria and marine biotechnology. In both cases the focus is on structure determination of enzymes which may explain 1) molecular mechanisms underlying iron sequestering and 2) identification of novel enzymes with commercial potential.

Highlights

Glycosylases structures

Team members

Elin Moe, PhD

Andreia Fernandes, PhD student

Filipe Rollo, PhD student (shared with Dr. Smilja Todorovic,

Carlota Conceição, PhD student (visitor from FCT)

Collaborations

Institut de Biologie Structurale (IBS), Grenoble, France.

Department of cancer research and molecular medicine, NTNU, Norway.

Department of Chemistry, UiT – the arctic university of Norway.

Egas Moniz – Cooperativa de Ensino Superior (CESEM) and UCIBIO@FCT UNL, Portugal.

Technische Universität Berlin, Germany.

Publications (2015 - 2022)

Moe E, Silveira CM, Zuccarello L, Rollo F, Stelter M, De Bonis S, Kulka-Peschke C, Katz S, Hildebrandt P, Zebger I, Timmins J, Todorovic S. Human endonuclease III/NTH1: focusing on the [4Fe-4S] cluster and the N-terminal domain. Chem Commun (Camb). 2022 Nov 10;58(90):12568-12571. [doi: 10.1039/d2cc03643f. PMID: 36279116].

Rollo F, Borges PT, Silveira CM, Rosa MTG, Todorovic S, Moe E. Disentangling Unusual Catalytic Properties and the Role of the [4Fe-4S] Cluster of Three Endonuclease III from the Extremophile D. radiodurans. Molecules. 2022 Jul 2;27(13):4270. doi: 10.3390/molecules27134270. PMID: 35807515; PMCID: PMC9268735.

Silveira, C. M., Moe, E., Fraaije, M., Martins, L. O., & Todorovic, S. (2020). Resonance Raman view of the active site architecture in bacterial DyP-type peroxidases. RSC Advances. https://doi.org/10.1039/d0ra00950d

Trindade, Inês B, Moe, E., & Louro, R. O. (2020). Siderophore‐Interacting Protein. In Encyclopedia of Inorganic and Bioinorganic Chemistry. https://doi.org/10.1002/9781119951438.eibc2743

Fonseca, B. M., Silva, L., Trindade, I. B., Moe, E., Matias, P. M., Louro, R. O., & Paquete, C. M. (2019). Optimizing Electroactive Organisms: The Effect of Orthologous Proteins. Frontiers in Energy Research, 7. https://doi.org/10.3389/fenrg.2019.00002

Trindade, I.B., Silva, J. M., Fonseca, B. M., Catarino, T., Fujita, M., Matias, P. M., Moe, E., & Louro, R. O. (2019). Structure and reactivity of a siderophore-interacting protein from the marine bacterium Shewanella reveals unanticipated functional versatility. Journal of Biological Chemistry, 294(1). https://doi.org/10.1074/jbc.RA118.005041

Sarre, A., Stelter, M., Rollo, F., De Bonis, S., Seck, A., Hognon, C., Ravanat, J.-L., Monari, A., Dehez, F., Moe, E., & Timmins, J. (2019). The three Endonuclease III variants of Deinococcus radiodurans possess distinct and complementary DNA repair activities. DNA Repair, 78. https://doi.org/10.1016/j.dnarep.2019.03.014

Frade, K. S. T., Fernandes, A. C. P., Silveira, C. M., Fraza-o, C., & Moe, E. (2018). A novel bacterial class v dye-decolourizing peroxidase from the extremophile Deinococcus radiodurans: Cloning, expression optimization, purification, crystallization, initial characterization and X-ray diffraction analysis. Acta Crystallographica Section F: Structural Biology Communications. https://doi.org/10.1107/S2053230X18008488

Moe, Elin, Rollo, F., Silveira, C. M., Sezer, M., Hildebrandt, P., & Todorovic, S. (2018). Spectroelectrochemical insights into structural and redox properties of immobilized endonuclease III and its catalytically inactive mutant. Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 188, 149–154. https://doi.org/10.1016/j.saa.2017.06.050

Timmins, J., & Moe, E. (2016). A decade of biochemical and structural studies of the DNA repair machinery of Deinococcus radiodurans: Major findings, functional and mechanistic insight and challenges. Computational and Structural Biotechnology Journal, 14, 168–176. https://doi.org/doi:10.1016/j.csbj.2016.04.001

Trindade, I.B., Fonseca, B. M., Matias, P. M., Louro, R. O., & Moe, E. (2016). A putative siderophore-interacting protein from the marine bacterium Shewanella frigidimarina NCIMB 400: Cloning, expression, purification, crystallization and X-ray diffraction analysis. Acta Crystallographica Section:F Structural Biology Communications, 72. https://doi.org/10.1107/S2053230X16011419

Niiranen, L., Lian, K., K., J., & Moe, E. (2015). Crystal structure determination of DNA polymerase III b-subunit from the extreme radiation and desiccation resistant bacterium Deinococcus radiodurans. BMC Structural Biology, 15:5. https://doi.org/DOI: 10.1186/s12900-015-0032-6

Lian, K., Leiros, H. K. S., & Moe, E. (2015). MutT from the fish pathogen Aliivibrio salmonicida is a cold-active nucleotide-pool sanitization enzyme with unexpectedly high thermostability. FEBS Open Bio, 5. https://doi.org/10.1016/j.fob.2015.01.006

Moe, E, Assefa, N. G., Leiros, I., Torseth, K. J., Smalås, A. O., & Willassen, N. P. (2015). Reduced Hydrophobicity of the Minor Groove Intercalation Loop is Critical for Efficient Catalysis by Cold Adapted Uracil-DNA N-Glycosylase from Atlantic Cod. J Thermodyn Catal, 6:155. https://doi.org/10.4172/2157-7544.1000155

Sarre, A., Ökvist, M., Klar, T., Hall, D. R., Smalås, A. O., McSweeney, S., Timmins, J., & Moe, E. (2015). Structural and functional characterization of two unusual endonuclease III enzymes from Deinococcus radiodurans. Journal of Structural Biology, 191(2). https://doi.org/10.1016/j.jsb.2015.05.009

Pedersen, H. L., Johnson, K. A., Mcvey, C. E., Leiros, I., & Moe, E. (2015). Structure determination of uracil-DNA N-glycosylase from Deinococcus radiodurans in complex with DNA. Acta Crystallographica Section D: Biological Crystallography, 71. https://doi.org/10.1107/S1399004715014157

Moe, E, Sezer, M., Hildebrandt, P., & Todorovic, S. (2015). Surface enhanced vibrational spectroscopic evidence for an alternative DNA-independent redox activation of endonuclease III. Chem Commun (Camb), 51(15), 3255–3257. https://doi.org/10.1039/c4cc09498k

Social Media / Lab website

https://www.itqb.unl.pt/researchers/elinmoe