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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

A single P115Q mutation modulates specificity in the Corynebacterium pseudotuberculosis arginine repressor

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Mariutti, Ricardo B. [1] ; Hernandez-Gonzalez, Jorge E. [2] ; Nascimento, Andrey F. Z. [3] ; de Morais, Mariana A. B. [3] ; Murakami, Mario T. [3] ; Carareto, Claudia M. A. [4] ; Arni, Raghuvir K. [2, 1]
Total Authors: 7
[1] UNESP, Multiuser Ctr Biomol Innovat, IBILCE, Sao Jose Do Rio Preto, SP - Brazil
[2] UNESP, Dept Phys, IBILCE, Sao Jose Do Rio Preto, SP - Brazil
[3] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Synchrotron Light Lab LNLS, Campinas, SP - Brazil
[4] UNESP, IBILCE, Lab Mol Evolut, Sao Jose Do Rio Preto, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Web of Science Citations: 0

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 angstrom 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. (AU)

FAPESP's process: 18/07977-3 - Structural biology, mechanisms and inhibitory strategies of proteins involved in the pathogenic dissemination.
Grantee:Ricardo Barros Mariutti
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 15/13765-0 - Structural Studies and Characterization of Proteins by X-ray Crystallography and Nuclear Magnetic Resonance. Structural investigations and biophysics of molecular mechanisms of functional proteins.
Grantee:Raghuvir Krishnaswamy Arni
Support Opportunities: Regular Research Grants
FAPESP's process: 16/19995-0 - Analysis of structural and functional diversity of GH43 enzymes from Xanthomonas axonopodis pv. citri: biological implications and potential biotechnological applications
Grantee:Mariana Abrahão Bueno de Morais
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 15/18868-2 - Multi-user equipment acquisition for molecular and structural biology
Grantee:Raghuvir Krishnaswamy Arni
Support Opportunities: Multi-user Equipment Program
FAPESP's process: 18/10736-8 - Protein exfoliative D (ETD) of Staphylococcus aureus: inactivation / activation by synthetic peptides and characterization of complexes
Grantee:Carolina Gismene
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 16/24587-9 - In silico identification of novel competitive and alosteric inhibitors of falcipains 2 and 3
Grantee:Jorge Enrique Hernández González
Support Opportunities: Scholarships in Brazil - Doctorate