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

Favela-Candia, Alejandro; Téllez‐Valencia, Alfredo; Campos-Almazán, Mara Ibeth; Sierra-Campos, Erick; Valdez-Solana, Mónica; Oria-Hernández, Jesús; Castillo-Villanueva, Adriana; Nájera, Hugo; Avitia-Domínguez, Claudia

doi:10.1007/s12033-019-00159-5

Cited by 5 publications

(4 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The previously reported SaSK 3D homology model [18] was employed for docking studies, the protein structure was prepared with the Protein Preparation Wizard in Maestro (Schrödinger Suite Release 2019-4) [37]. Bonds order was assigned, hydrogen atoms were added, and formal charges were treated, protein minimization was applied with the OPLS3e forcefield.…”

Section: Docking Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Finding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant Staphylococcus aureus through Computer-Assisted Drug Design

et al. 2021

Self Cite

View full text Add to dashboard Cite

Methicillin-resistant Staphylococcus aureus (MRSA) is an important threat as it causes serious hospital and community acquired infections with deathly outcomes oftentimes, therefore, development of new treatments against this bacterium is a priority. Shikimate kinase, an enzyme in the shikimate pathway, is considered a good target for developing antimicrobial drugs; this is given because of its pathway, which is essential in bacteria whereas it is absent in mammals. In this work, a computer-assisted drug design strategy was used to report the first potentials inhibitors for Shikimate kinase from methicillin-resistant Staphylococcus aureus (SaSK), employing approximately 5 million compounds from ZINC15 database. Diverse filtering criteria, related to druglike characteristics and virtual docking screening in the shikimate binding site, were performed to select structurally diverse potential inhibitors from SaSK. Molecular dynamics simulations were performed to elucidate the dynamic behavior of each SaSK–ligand complex. The potential inhibitors formed important interactions with residues that are crucial for enzyme catalysis, such as Asp37, Arg61, Gly82, and Arg138. Therefore, the compounds reported provide valuable information and can be seen as the first step toward developing SaSK inhibitors in the search of new drugs against MRSA.

show abstract

Section: Docking Studiesmentioning

confidence: 99%

“…In 2019, our group reported the biochemical, kinetic, and structural characterization of SK from MRSA (SaSK). In that work, it was found that SaSK shares common characteristics with other bacterial SKs, and by performing homology modeling and molecular dynamics studies important structural information was reported [18].…”

Section: Introductionmentioning

confidence: 99%

Finding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant Staphylococcus aureus through Computer-Assisted Drug Design

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…This enzyme belongs to the family of nucleoside monophosphate (NMP) kinases, a subfamily of the P-loop including the nucleoside triphosphate hydrolase superfamily [120,121]. This family Shikimate kinase (SK), the fifth enzyme in the shikimate pathway (Figure 1), catalyzes the conversion of SHK into shikimate-3-phosphate (S3P) using adenosine 5 -triphosphate (ATP) as the co-substrate.…”

Section: Shikimate Kinase (Arok Coding Sequence; Ec 27171)mentioning

confidence: 99%

Section: Shikimate Kinase (Arok Coding Sequence; Ec 27171)mentioning

confidence: 99%

Mycobacterium tuberculosis Shikimate Pathway Enzymes as Targets for the Rational Design of Anti-Tuberculosis Drugs

et al. 2020

View full text Add to dashboard Cite

Roughly a third of the world’s population is estimated to have latent Mycobacterium tuberculosis infection, being at risk of developing active tuberculosis (TB) during their lifetime. Given the inefficacy of prophylactic measures and the increase of drug-resistant M. tuberculosis strains, there is a clear and urgent need for the development of new and more efficient chemotherapeutic agents, with selective toxicity, to be implemented on patient treatment. The component enzymes of the shikimate pathway, which is essential in mycobacteria and absent in humans, stand as attractive and potential targets for the development of new drugs to treat TB. This review gives an update on published work on the enzymes of the shikimate pathway and some insight on what can be potentially explored towards selective drug development.

show abstract

Glycosylation, Sulfation and Phosphorylation

Křen

2020

Applied Biocatalysis

View full text Add to dashboard Cite

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

Cited by 5 publications

References 56 publications

Finding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant Staphylococcus aureus through Computer-Assisted Drug Design

Finding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant Staphylococcus aureus through Computer-Assisted Drug Design

Mycobacterium tuberculosis Shikimate Pathway Enzymes as Targets for the Rational Design of Anti-Tuberculosis Drugs

Glycosylation, Sulfation and Phosphorylation

Contact Info

Product

Resources

About