6WJO

Crystal structure of wild-type Arginine Repressor from the pathogenic bacterium Corynebacterium pseudotuberculosis bound to tyrosine

Summary for 6WJO

• Entry DOI: 10.2210/pdb6wjo/pdb
• Descriptor: Arginine repressor, TYROSINE, SULFATE ION, ... (5 entities in total)
• Functional Keywords: enzyme specificity, dna binding protein
• Biological source: Corynebacterium pseudotuberculosis (strain C231)
• Total number of polymer chains: 2
• Total formula weight: 18182.46

Authors

Nascimento, A.F.Z.,Hernandez-Gonzalez, J.E.,de Morais, M.A.B.,Murakami, M.T.,Carareto, C.M.A.,Arni, R.K.,Mariutti, R.B. (deposition date: 2020-04-14, release date: 2020-04-22, Last modification date: 2023-10-18)

Primary citation

Mariutti, R.B.,Hernandez-Gonzalez, J.E.,Nascimento, A.F.Z.,de Morais, M.A.B.,Murakami, M.T.,Carareto, C.M.A.,Arni, R.K.
A single P115Q mutation modulates specificity in the Corynebacterium pseudotuberculosis arginine repressor.
Biochim Biophys Acta Gen Subj, 1864:129597-, 2020

PubMed Abstract: The arginine repressor (ArgR) regulates the expression of genes involved in arginine biosynthesis. Upon attaining a threshold concentration of arginine in the cytoplasm, the trimeric C-terminal domain of ArgR binds three arginines in a shallow surface cleft and subsequently hexamerizes forming a dimer of trimers containing six Arg co-repressor molecules which are buried at the subunit interfaces. The N-terminal domains of this complex bind to the DNA promoter thereby interrupting the transcription of the genes related to Arg biosynthesis. The crystal structures of the wild type and mutant Pro115Gln ArgR from Corynebacterium pseudotuberculosis determined at 1.7 Å demonstrate that a single amino acid substitution switches co-repressor specificity from Tyr to Arg. Molecular dynamics simulations indicate that the first step, i.e., the binding of the co-repressor, occurs in the trimeric state and that Pro115Gln ArgR preferentially binds Arg. It was also shown that, in Pro115 ArgR hexamers, the concomitant binding of sodium ions shifts selectivity to Tyr. Structural data combined with phylogenetic analyses of ArgR from C. pseudotuberculosis suggest that substitutions in the binding pocket at position 115 may alter its specificity for amino acids and that the length of the protein interdomain linker can provide further functional flexibility. These results support the existence of alternative ArgR regulatory mechanisms in this pathogenic bacterium.

PubMed: 32156582
DOI: 10.1016/j.bbagen.2020.129597

Experimental method

X-RAY DIFFRACTION (1.693 Å)