Structure-based virtual screening and biological evaluation of Mycobacterium tuberculosis adenosine 5'-phosphosulfate reductase inhibitors.
Tuberculosis is among the world's deadliest infectious diseases. APS reductase catalyzes the first committed step in bacterial sulfate reduction and is a validated drug target against latent tuberculosis infection. We performed a virtual screening to identify APSR inhibitors. These inhibitors represent the first non-phosphate-based molecules to inhibit APSR. Common chemical features lay the foundation for the development of agents that could shorten the duration of chemotherapy by targeting the latent stage of TB infection.
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Sandro
S
Cosconati
Jiyoung A
JA
Hong
Ettore
E
Novellino
Kate S
KS
Carroll
David S
DS
Goodsell
Arthur J
AJ
Olson
D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D008024:Ligands; D050862:Oxidoreductases Acting on Sulfur Group Donors; C019618:adenylylsulfate reductase