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Biochemistry of bacterial respiratory chain protein elucidated

Oeiras, 20.10.2015

Rational drug design requires thorough biochemical knowledge of drug targets. In their most recent work, researchers from the Biological Energy Transduction and the Membrane Protein Crystallography Labs looked into how a respiratory chain enzyme, from the pathogenic bacteria Staphylococcus aureus, interacts with its substrates. The results are published in the latest issue of Molecular Microbiology and are highlighted on the journal’s cover.

The rise of multidrug-resistant bacteria, specifically among Staphylococcus aureus, has prompted the search for new targets for antibiotic action. Type-II NADH:quinone oxidoreductases are promising new targets for antibiotics: these membrane proteins involved in respiratory chains are absent in mammals and present in some pathogenic bacteria.

Type-II NADH:quinone oxidoreductase (NDH-2) catalyses the transfer of two electrons from NADH to quinone, indirectly contributing to the difference potential across the bacterial membrane. The structural and biochemical studies conducted in this work reveal that NDH-2 is a dimeric protein with distinct binding sites for its two substrates: NADH and quinones. Kinetic studies identify quinone reduction as the rate limiting step.

The study published in Molecular Microbiology results from a collaboration between researchers at ITQB, FCT-UNL and Technische Universität München (Germany)/Medical University of Graz (Austria).



Original article

Molecular Microbiology (2015) 98(2): 272–288

Type-II NADH:quinone oxidoreductase from Staphylococcus aureus has two distinct binding sites and is rate limited by quinone reduction

Filipa V. Sena1, Ana P. Batista1, Teresa Catarino1,2, José A. Brito1, Margarida Archer1, Martin Viertler3,4,5, Tobias Madl3,4,5, Eurico J. Cabrita6 and Manuela M. Pereira1


2./6. Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa
3./4./5. Technische Universität München, Germany/Medical University of Graz, (Austria)



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