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TitleA counter-enzyme complex regulates glutamate metabolism in Bacillus subtilis.
Journal, issue, pagesNat Chem Biol, Vol. 18, Issue 2, Page 161-170, Year 2022
Publish dateDec 20, 2021
AuthorsVijay Jayaraman / D John Lee / Nadav Elad / Shay Vimer / Michal Sharon / James S Fraser / Dan S Tawfik /
PubMed AbstractMulti-enzyme assemblies composed of metabolic enzymes catalyzing sequential reactions are being increasingly studied. Here, we report the discovery of a 1.6 megadalton multi-enzyme complex from ...Multi-enzyme assemblies composed of metabolic enzymes catalyzing sequential reactions are being increasingly studied. Here, we report the discovery of a 1.6 megadalton multi-enzyme complex from Bacillus subtilis composed of two enzymes catalyzing opposite ('counter-enzymes') rather than sequential reactions: glutamate synthase (GltAB) and glutamate dehydrogenase (GudB), which make and break glutamate, respectively. In vivo and in vitro studies show that the primary role of complex formation is to inhibit the activity of GudB. Using cryo-electron microscopy, we elucidated the structure of the complex and the molecular basis of inhibition of GudB by GltAB. The complex exhibits unusual oscillatory progress curves and is necessary for both planktonic growth, in glutamate-limiting conditions, and for biofilm growth, in glutamate-rich media. The regulation of a key metabolic enzyme by complexing with its counter enzyme may thus enable cell growth under fluctuating glutamate concentrations.
External linksNat Chem Biol / PubMed:34931064 / PubMed Central
MethodsEM (single particle)
Resolution2.42 - 3.9 Å
Structure data

23817

7mfm

EMDB-23817, PDB-7mfm:
Glutamate synthase, glutamate dehydrogenase counter-enzyme complex
Method: EM (single particle) / Resolution: 2.42 Å

23825

7mft

EMDB-23825, PDB-7mft:
Glutamate synthase, glutamate dehydrogenase counter-enzyme complex (GudB6-GltA6-GltB6)
Method: EM (single particle) / Resolution: 3.9 Å

Chemicals

ChemComp-FMN:
FLAVIN MONONUCLEOTIDE

ChemComp-F3S:
FE3-S4 CLUSTER

ChemComp-FAD:
FLAVIN-ADENINE DINUCLEOTIDE / FAD*YM

ChemComp-SF4:
IRON/SULFUR CLUSTER

Source
  • bacillus subtilis (bacteria)
  • bacillus subtilis subsp. subtilis ncib 3610 = atcc 6051 = dsm 10 (bacteria)
KeywordsCYTOSOLIC PROTEIN / Counter-enzyme complex / glutamate synthase / glutamate dehydrogenae

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