Miguel Teixeira Lab
Functional Biochemistry of Metalloenzymes
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The main research themes of the Laboratory are the study at the molecular level of the structure and functional mechanisms of soluble metalloenzymes, namely those involved in oxygen and nitric oxide metabolisms. |
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Miguel Sepúlveda Teixeira Phone (+351) 214469322 | Extension 1322 |
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Research Interests
The appearance of oxygen in the earth atmosphere ca 2.5 Gy ago introduced a huge challenge for life. Oxygen, when directly reduced to water by respiratory enzymes, namely the haem-copper oxygen reductases, allows energy conservation and the extraction of maximal energy from the reduced organic compounds; but if reduction of oxygen occurs stepwise, in a non-controlled way, it leads to the formation of reactive oxygen species, such as the superoxide anion or hydrogen peroxide, which are highly deleterious to all life forms.
In this laboratory, we study mainly metalloenzymes involved in oxygen biochemistry. One such example are the flavodiiron proteins, which have oxygen and/or nitric oxide reductase activities, and are widespread among the three life kingdoms. These enzymes play an essential role in protecting both aerobic and anaerobic organisms from oxygen itself, by reducing it to water and thereby avoiding the formation of ROS. Moreover, they also play a key role in host-pathogen interactions, by combating the nitrosative stress imposed by the innate immune system of the hosts. Our present objectives in this area are twofold: establish the molecular mechanism of the reaction and understand what dictates the preference towards O2 or NO, by analysing wild type and site directed mutants and enzyme constructs. Another example are the superoxide reductases, which reduce oxygen to hydrogen peroxide. The three-dimensional structures of several of these enzymes have been determined in a collaboration between our group and the ITQB Macromolecular Crystallography Unit.
More recently, enzymes endowed with hydrogen peroxide reductase activity are also being studied. These enzymes contain a di-iron site, where the reaction takes place, but the molecular mechanism remains to be established, and is one of our aims.
These studies are being pursued using a large array of complementary biochemical and spectroscopic methods, and in collaboration with several groups either at ITQB, or through International cooperations, which also involve the study of several other metalloproteins.
Group Members
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Filipe Folgosa, PhD, Researcher
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Maria C. Martins, PhD Student
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Susana Fernandes, PhD Student
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Catarina Alves, PhD Student
Selected Publications
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Structural basis for energy transduction by respiratory alternative complex III, Sousa, JS, Calisto, F., Langer, JD, Mills, DJ, Refojo, PN, Teixeira,M, Kühlbrandt, W, Vonck, J, Pereira, MM, Nature Commun, 2018, 30, 1728
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The multidomain flavodiiron protein from Clostridium difficile 630 is an NADH:oxygen oxidoreductase, Folgosa, F, Martins, MC, Teixeira, M, 2018, , Sci. Rep., 8, 10164.
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How the Anaerobic Enteropathogen Clostridioides difficile Tolerates Low O2 Tensions, Kint N, Alves Feliciano C, Martins MC, Morvan C, Fernandes SF, Folgosa F, Dupuy B, Texeira M, Martin-Verstraete I, mBio 2020 11 (5): e01559-20. doi: 10.1128/mBio.01559-20
Laboratory's Website
For further information please visit the laboratory's website
Bioquímica Funcional de Metaloenzimas
O aparecimento do oxigénio há cerca de 2.5 Giga anos introduziu um enorme desafio para os seres vivos. O oxigénio, quando reduzido directamente a água por enzimas respiratórias, em particular pelas reductases de oxigénio de hemo-cobre, permite a conservação de energia. Por outro lado, se a redução do oxigénio ocorrer passo a passo, de modo não controlado, formam-se espécies reactivas de oxigénio, como o anião superóxido e o peróxido de hidrogénio, bastante prejudiciais a todos os seres vivos.
Neste Laboratório estudam-se, entre outras, metaloenzimas envolvidas nos dois aspectos da bioquímica do oxigénio: reductases de oxigénio, e reductases de superóxido e peróxido de hidrogénio, citoplasmáticas.
