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bioRxiv · 10.1101/2020.11.14.381715

3D architecture and structural flexibility revealed in the subfamily of large glutamate dehydrogenases by a mycobacterial enzyme

Lazaro, M.·Melero, R.·Huet, C.·Lopez-Alonso, J. P.·Delgado, S.·Dodu, A.·Bruch, E. M.·Abriata, L. A.·Alzari, P. M.·Valle, M.·Lisa, M.-N.
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Abstract

Glutamate dehydrogenases (GDHs) are widespread metabolic enzymes that play key roles in nitrogen homeostasis. Large glutamate dehydrogenases composed of 180 kDa subunits (L-GDHs180) contain long N- and C-terminal segments flanking the catalytic core. Despite the relevance of L-GDHs180 in bacterial physiology, the lack of structural data for these enzymes has limited the progress of functional studies. Here we show that the mycobacterial L-GDH180 (mL-GDH180) adopts a quaternary structure that is radically different from that of related low molecular weight enzymes. Intersubunit contacts in mL-GDH180 involve a C-terminal domain that we propose as a new fold and a flexible N-terminal segment comprising ACT-like and PAS-type domains that could act as metabolic sensors for allosteric regulation. These findings uncover unique aspects of the structure-function relationship in the subfamily of L-GDHs.

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Lazaro, M., Melero, R., Huet, C., Lopez-Alonso, J. P., Delgado, S., Dodu, A., Bruch, E. M., Abriata, L. A., Alzari, P. M., Valle, M., Lisa, M.-N.. 2020-11-15. 3D architecture and structural flexibility revealed in the subfamily of large glutamate dehydrogenases by a mycobacterial enzyme. https://doi.org/10.1101/2020.11.14.381715

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