Smilja Todorovic Lab

	We are interested in fundamental questions and biotechnological applications of metalloproteins that carry out catalysis, detoxification, signaling, electron transfer and DNA repair. We study their mechanistic properties and immobilize them on tailored plasmonic metal hybrids to probe molecular processes at interfaces or construct biosensing devices. We use advanced vibrational spectroscopy, electrochemistry and spectroelectrochemistry as the main tools in our research.
	Smilja Todorovic Principal Investigator PhD in 2000, Belgrade University, Serbia Mayo Clinic Graduate school, USA Phone (+351) 214469717 | Extension 1717 Email smilja@itqb.unl.pt

Research Interests

Spectroscopy, structure and function: We use physical tools, vibrational spectroscopy, electrochemistry and spectroelectrochemistry, to investigate biophysico-chemical properties of heme, non-hemic iron, Fe-S and Cu containing metalloproteins with distinct cellular functions. Metal centers constitute active sites of over one third of all enzymes and we aim at understanding how different proteins fine-tune the reactivity of their metal cofactors and how such metal centers help to tailor the dynamics and stability of protein molecules.

Spectroscopy of immobilized metalloproteins and applications: By wiring enzymes to biocompatible conductive supports (i.e. electrodes), we design metalloenzyme-electrode constructs to study molecular processes at interfaces, which are ubiquitous in biology and also constitute the basis for the functioning of biosensoric devices.

We monitor structural properties and interactions of immobilized metalloenzymes by surface enhanced resonance Raman (SERR) and IR (SEIRA) spectro-electrochemistry and catalysis by electrochemistry. We study enzymes that

1. are interesting for development of biosensors, e.g. DyP and micro-peroxidases; we can take advantage of the high specificity of enzymatic reactions to detect the enzyme substrate and monitor the structure of the biocatalyst along the catalytic reaction;
2. exert their function in conditions of restricted motion, such as membrane proteins;
3. can be co-immobilized with substrate / physiological redox partners, e.g. DNA : DNA glycosylases.

Spectroscopy of cells: We are also interested in Label-free chemical imaging of cells, which is based on specific Raman fingerprint of biomolecules as well as in surface enhanced Raman (SER) detection of viruses and bacteria. 

Group Members

• Célia Silveira, Researcher

• Lidia Zuccarello, Post-doc Fellow

• Filipe Rollo, PhD student (supervision with Elin Moe)

• Catarina Barbosa, PhD student

• Edilson Galdino, BI fellow

Selected Publications

1. Pelmenschikov, V.;  Ferreira, D.; Venceslau, S. S.; Hildebrandt, P.; Pereira, I. A. C.; Todorovic, S. 2023 ´Substrate-Dependent Conformational Switch of the Noncubane [4Fe-4S] Cluster in Heterodisulfide Reductase HdrB´ J. Am. Chem. Soc. 145, 7−11

2. Moe, E.; Silveira, C. M.; Zuccarello, L.; Rollo, F., Stelter, M.; De Bonis, S.; Kulka-Peschke, C.; Katz, S.; Hildebrandt, P.; Zebger, I.; Timmins, J.; Todorovic, S. 2022 ´Human endonuclease III/NTH1: focusing on the [4Fe–4S] cluster and the N-terminal domain´ Chem. Commun. 58,12568 -12571

3. Caserta, G.; Zuccarello, L.; Barbosa, C.; Silveira, C. M.; Moe, E., Katz S.; Hildebrandt, P.;  Zebger I., Todorovic, S. 2022 ´Unusual structures and unknown roles of FeS clusters in metalloenzymes seen from a resonance Raman spectroscopic perspective´ Coordination Chemistry Reviews 452 214287

4. Barbosa, C.; Silveira, C. M.;  Silva, D.; Brissos, V.; Hildebrandt, P.; Martins, L. O.; Todorovic, S. 2020 ´Immobilized dye-decolorizing peroxidase (DyP) and directed evolution variants for hydrogen peroxide biosensing´ Biosensors and Bioelectronics 153, 112055

Laboratory's Website

For further information visit the laboratory's website

BioEspectroscopia de Raman (PT)

Estamos interessados em questões fundamentais e aplicações biotecnológicas de metaloproteínas envolvidas em reacções de catálise, destoxificação, sinalização, transferência electrónica e reparação de DNA. Estudamos as propriedades mecanísticas destas metaloproteínas e imobilizamo-las em híbridos proteína-metal plasmónico para estudar os seus processos moleculares em interfaces ou para construir biossensores. Utilizamos espectroscopias vibracionais avançadas, electroquímica e espectroelectroquímica como principais ferramentas.

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