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Structure–function studies on the complex iron–sulfur flavoprotein glutamate synthase: the key enzyme of ammonia assimilation

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Abstract

Glutamate synthases are complex iron–sulfur flavoproteins that participate in the essential ammonia assimilation pathway in microorganisms and plants. The recent determination of the 3-dimensional structures of the α subunit of the NADPH-dependent glutamate synthase form and of the ferredoxin-dependent enzyme of Synechocystis sp. PCC 6803 provides a framework for the interpretation of the functional properties of these enzymes, and highlights protein segments most likely involved in control and coordination of the partial catalytic activities of glutamate synthases, which take place at sites distant from each other in space. In this review, we focus on the current knowledge on structure–function relationships in glutamate synthases, and we discuss open questions on the mechanisms of control of the enzyme reaction and of electron transfer among the enzyme flavin cofactors and iron–sulfur clusters.

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Abbreviations

2-IG:

2-iminoglutarate

2-OG:

2-oxoglutarate

DHODH:

dihydroorotate dehydrogenase

DPD:

dihydropyrimidine dehydrogenase

Em :

mid-point potential

FAD:

flavin adenin dinucleotide

flavin (FMN FAD)hq :

hydroquinone form of flavin FMN or FAD

Flavin (FMN FAD)sq :

semiquinone form of flavin (FMN or FAD)

FMN:

flavin mononucleotide

GAT:

glutamine amidotransferase

L-DON:

6-diazo-5-oxo-L-norleucine

L-MetS:

L-methionine sulfone

NAD(P)H-GltS, Fd-GltS:

NAD(P)H- or ferredoxin-dependent glutamate synthase

Ntn:

N-terminal nucleophile

ONL:

5-oxo-L-norleucine

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Authors and Affiliations

  1. Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, Via Celoria 26, Milano, Italy, 20131

    Maria A. Vanoni, Laura Dossena & Bruno Curti

  2. Department of Biomolecular Mass Spectrometry, Bijovet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Sorbonnelaan 16, Utrecht, CA, The Netherlands

    Robert H. H. van den Heuvel

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  1. Maria A. Vanoni
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  2. Laura Dossena
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  3. Robert H. H. van den Heuvel
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  4. Bruno Curti
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Correspondence to Maria A. Vanoni.

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Vanoni, M.A., Dossena, L., Heuvel, R.H.H.v. et al. Structure–function studies on the complex iron–sulfur flavoprotein glutamate synthase: the key enzyme of ammonia assimilation. Photosynth Res 83, 219–238 (2005). https://doi.org/10.1007/s11120-004-2438-z

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