scholarly journals Slow-Binding Inhibition of Mycobacterium tuberculosis Shikimate Kinase by Manzamine Alkaloids

Biochemistry ◽  
2018 ◽  
Vol 57 (32) ◽  
pp. 4923-4933 ◽  
Author(s):  
Johayra Simithy ◽  
Ngolui Rene Fuanta ◽  
Mansour Alturki ◽  
Judith V. Hobrath ◽  
Amir E. Wahba ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Shikimate Kinase ◽  
Binding Inhibition ◽  
Manzamine Alkaloids

Mechanism of Phosphoryl Transfer Catalyzed by Shikimate Kinase from Mycobacterium tuberculosis

2006 ◽  
Vol 364 (3) ◽  
pp. 411-423 ◽  
Author(s):  
Marcus D. Hartmann ◽  
Gleb P. Bourenkov ◽  
Attila Oberschall ◽  
Nicolai Strizhov ◽  
Hans D. Bartunik
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Phosphoryl Transfer ◽  
Shikimate Kinase

scholarly journals Virtual Screening, Molecular Docking and Dynamic Simulation of Shikimate Kinase from Mycobacterium Tuberculosis Using in Silico Approach

2020 ◽  
Author(s):  
Dr. Mustafa Alhaji Isa
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Docking ◽  
Binding Site ◽  
Md Simulation ◽  
Simulation Analysis ◽  
3D Structure ◽  
Normal Function ◽  
Binding Energies ◽  
Shikimate Kinase ◽  
Lipinski’S Rule

<p>Shikimate kinase (SK) is an enzyme that catalyzes the fifth steps in the shikimate pathway. The enzyme facilitate the transfer of phosphoryl from ATP to shikimate, to produce ADP and shikimate-3-phosphate from <i>Mycobacterium tuberculosis</i> (MTB). The 3D structure of SK bound ligands (4-(2-Hydroxyethyl)-1-Piperazine Ethanesulfonic Acid (EPE)), ADP and metals (Mg2+, Cl- and Pt+) obtained from PDB (PDB ID: 1L4U and resolution 1.8Å). The structural analysis of the SK revealed that it has a substrate or shikimate binding site (Asp34, Arg58, and Lys136) and substrate binding via amide nitrogen (Gly80). It also possessed nucleotide binding region (Gly12─Thr17), the ATP binding site (Arg117 and Arg153) and metallic ion (Mg2+) binding site (Ser16 and Asp32). All these residues mentioned above play an essential role in the catalytic activity of the SK. Therefore inhibition any of these residues serve as a stumbling block for the normal function of the enzyme. A total of eleven thousand three hundred and twenty-three (11323) compounds obtained from two public databases (Zinc Database and PubChem) capable of binding to SK with good binding affinities. These compounds further filtered for Lipinski’s rule of five, drug-likeness, molecular docking analysis, and ADME and toxicity analysis. Three compounds with minimum binding energies─ PubChem15478 (─11.75 kcal/mol), ZINC02838601 (─11.52 kcal/mol), and ZINC11790367 (─9.88 kcal/mol) ─were selected and used for the MD simulation analysis. Also, MD simulation of the SK bound to EPE, ADP, and Mg2+ were carried out to compare their stabilities with the selected protein-ligand complexes. The result showed that the two compounds (ZINC11790367 and PubChem15478) formed stable and rigid complexes comparable to the bound ligand and the cofactors during the 50ns MD simulation. Therefore, it concluded that the above mentioned two compounds capable of inhibiting SK considered as prospective drugs for MTB after successful experimental validation.</p>

Screening of antitubercular compound library identifies novel shikimate kinase inhibitors of Mycobacterium tuberculosis

2016 ◽  
Vol 100 (12) ◽  
pp. 5415-5426 ◽  
Author(s):  
Vikrant S. Rajput ◽  
Rukmankesh Mehra ◽  
Sanjay Kumar ◽  
Amit Nargotra ◽  
Parvinder Pal Singh ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Kinase Inhibitors ◽  
Compound Library ◽  
Shikimate Kinase

scholarly journals Mechanism of irreversible inhibition of Mycobacterium tuberculosis shikimate kinase by ilimaquinone

2018 ◽  
Vol 1866 (5-6) ◽  
pp. 731-739 ◽  
Author(s):  
Johayra Simithy ◽  
Ngolui Rene Fuanta ◽  
Judith V. Hobrath ◽  
Anna Kochanowska-Karamyan ◽  
Mark T. Hamann ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Shikimate Kinase ◽  
Irreversible Inhibition
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