7mft | pdb_00007mft
Glutamate synthase, glutamate dehydrogenase counter-enzyme complex (GudB6-GltA6-GltB6)
Structural highlights
FunctionGUDB_BACSU GudB seems to be intrinsically inactive, however spontaneous mutations removing a 9-bp direct repeat within the wild-type gudB sequence activated the GudB protein and allowed more-efficient utilization of amino acids of the glutamate family. This insertion presumably causes severe destabilization of the fold of the protein, leading to an inactive enzyme that is very quickly degraded. The cryptic GudB serves as a buffer that may compensate for mutations in the rocG gene and that can also be decryptified for the utilization of glutamate as a single carbon source in the absence of arginine. It is unable to synthesize glutamate.[1] [2] Publication Abstract from PubMedMulti-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. A counter-enzyme complex regulates glutamate metabolism in Bacillus subtilis.,Jayaraman V, Lee DJ, Elad N, Vimer S, Sharon M, Fraser JS, Tawfik DS Nat Chem Biol. 2022 Feb;18(2):161-170. doi: 10.1038/s41589-021-00919-y. Epub 2021 , Dec 20. PMID:34931064[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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