title: Isocitrate lyase of Mycobacterium tuberculosis is inhibited by quercetin through binding at N-terminus.
abstract: Combating tuberculosis requires new therapeutic strategies that not only target the actively dividing bacilli but also the dormant bacilli during persistent infection. Isocitrate lyase (ICL) is a key enzyme of the glyoxylate shunt, crucial for the survival of bacteria in macrophages and mice. MtbICL is considered as one of the potential and attractive drug targets against persistent infection. We report the inhibition of MtbICL by quercetin with IC50 of 3.57 μM. In addition, quercetin strongly inhibited the growth of Mtb H37Rv utilizing acetate, rather than glucose as the sole carbon source, suggesting the inhibition of glyoxylate shunt. Quercetin binds at the N-terminus of MtbICL (Kd - 6.68 μM).
authors: Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow 226 031, India.
authors: Harish
authors: H
authors: Shukla
authors: Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow 226 031, India.
authors: Vikash
authors: V
authors: Kumar
authors: Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow 226 031, India.
authors: Amit Kumar
authors: AK
authors: Singh
authors: Microbiology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow 226 031, India.
authors: Shivangi
authors: S
authors: Rastogi
authors: Microbiology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow 226 031, India.
authors: Shaheb Raj
authors: SR
authors: Khan
authors: Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow 226 031, India; Academy of Scientific and Innovative Research, Chennai 600 113, India.
authors: Mohammad Imran
authors: MI
authors: Siddiqi
authors: Microbiology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow 226 031, India; Academy of Scientific and Innovative Research, Chennai 600 113, India.
authors: Manju Yasoda
authors: MY
authors: Krishnan
authors: Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow 226 031, India; Academy of Scientific and Innovative Research, Chennai 600 113, India. Electronic address: sohail@cdri.res.in.
authors: Md Sohail
authors: MS
authors: Akhtar
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D007522:Isocitrate Lyase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011794:Quercetin / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011794:Quercetin; D007522:Isocitrate Lyase
keywords: Docking; Glyoxylate shunt; Isocitrate lyase; Mycobacteria; Quercetin