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Biochemical, Kinetic, and Computational Structural Characterization of Shikimate Kinase from Methicillin-Resistant Staphylococcus aureus

  • Alejandro Favela-Candia
  • Alfredo Téllez-Valencia
  • Mara Campos-Almazán
  • Erick Sierra-Campos
  • Mónica Valdez-Solana
  • Jesús Oria-Hernández
  • Adriana Castillo-Villanueva
  • Hugo Nájera
  • Claudia Avitia-DomínguezEmail author
Original Paper

Abstract

One of the most widespread pathogens worldwide is methicillin-resistant Staphylococcus aureus, a bacterium that provokes severe life-threatening illnesses both in hospitals and in the community. The principal challenge lies in the resistance of MRSA to current treatments, which encourages the study of different molecular targets that could be used to develop new drugs against this infectious agent. With this goal, a detailed characterization of shikimate kinase from this microorganism (SaSK) is described. The results showed that SaSK has a Km of 0.153 and 224 µM for shikimate and ATP, respectively, and a global reaction rate of 13.4 µmol/min/mg; it is suggested that SaSK utilizes the Bi–Bi Ping Pong reaction mechanism. Furthermore, the physicochemical data indicated that SaSK is an unstable, hydrophilic, and acidic protein. Finally, structural information showed that SaSK presented folding that is typical of its homologous counterparts and contains the typical domains of this family of proteins. Amino acids that have been shown to be important for SaSK protein function are conserved. Therefore, this study provides fundamental information that may aid in the design of inhibitors that could be used to develop new antibacterial agents.

Keywords

MRSA Shikimate kinase Enzyme kinetics Homology modeling Molecular dynamics 

Notes

Acknowledgements

C.A.D. and A.T.V. acknowledge Consejo Nacional de Ciencia y Tecnología (CONACyT) for Grants Nos. 258694 and 257848. CONACyT is also acknowledged for the fellowship granted to A.F.C. (No. 326106).

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Alejandro Favela-Candia
    • 1
  • Alfredo Téllez-Valencia
    • 1
  • Mara Campos-Almazán
    • 1
  • Erick Sierra-Campos
    • 2
  • Mónica Valdez-Solana
    • 2
  • Jesús Oria-Hernández
    • 3
  • Adriana Castillo-Villanueva
    • 3
  • Hugo Nájera
    • 4
  • Claudia Avitia-Domínguez
    • 1
    Email author
  1. 1.Facultad de Medicina y NutriciónUniversidad Juárez del Estado de DurangoDurangoMexico
  2. 2.Facultad de Ciencias QuímicasUniversidad Juárez del Estado de DurangoDurangoMexico
  3. 3.Laboratorio de Bioquímica Genética, Secretaría de SaludInstituto Nacional de PediatríaCiudad de MéxicoMexico
  4. 4.Departamento de Ciencias NaturalesUniversidad Autónoma Metropolitana, Unidad Cuajimalpa, Delegación Cuajimalpa de MorelosCiudad de MéxicoMexico

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