{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gupta P"],"funding":["NIAID NIH HHS","National Institutes of Health","Bill and Melinda Gates Foundation","Wellcome Trust","NIGMS NIH HHS"],"pagination":["3491-3506"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8220418"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19"],"pubmed_abstract":["The L-arginine biosynthesis pathway consists of eight enzymes that catalyse the conversion of L-glutamate to L-arginine. Arginine auxotrophs (argB/argF deletion mutants) of <i>Mycobacterium tuberculosis</i> are rapidly sterilised in mice, while inhibition of ArgJ with Pranlukast was found to clear chronic <i>M. tuberculosis</i> infection in a mouse model. Enzymes in the arginine biosynthetic pathway have therefore emerged as promising targets for anti-tuberculosis drug discovery. In this work, the ligandability of four enzymes of the pathway ArgB, ArgC, ArgD and ArgF is assessed using a fragment-based approach. We identify several hits against these enzymes validated with biochemical and biophysical assays, as well as X-ray crystallographic data, which in the case of ArgB were further conf"],"journal":["Computational and structural biotechnology journal"],"pubmed_title":["A fragment-based approach to assess the ligandability of ArgB, ArgC, ArgD and ArgF in the L-arginine biosynthetic pathway of &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt;."],"pmcid":["PMC8220418"],"funding_grant_id":["200814","SC1 GM140968","R37 AI026170","200814/Z/16/Z"],"pubmed_authors":["Thomas SE","Jacobs WR","Zaidan SA","Burgess A","Pasillas MA","Tiwari S","Mendes V","Cattermole E","Blundell TL","Cory-Wright J","Abell C","Meghir C","Coyne AG","Sebastian-Perez V","Gupta P"],"additional_accession":[]},"is_claimable":false,"name":"A fragment-based approach to assess the ligandability of ArgB, ArgC, ArgD and ArgF in the L-arginine biosynthetic pathway of &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt;.","description":"The L-arginine biosynthesis pathway consists of eight enzymes that catalyse the conversion of L-glutamate to L-arginine. Arginine auxotrophs (argB/argF deletion mutants) of <i>Mycobacterium tuberculosis</i> are rapidly sterilised in mice, while inhibition of ArgJ with Pranlukast was found to clear chronic <i>M. tuberculosis</i> infection in a mouse model. Enzymes in the arginine biosynthetic pathway have therefore emerged as promising targets for anti-tuberculosis drug discovery. In this work, the ligandability of four enzymes of the pathway ArgB, ArgC, ArgD and ArgF is assessed using a fragment-based approach. We identify several hits against these enzymes validated with biochemical and biophysical assays, as well as X-ray crystallographic data, which in the case of ArgB were further conf","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021","modification":"2026-05-08T18:55:30.292Z","creation":"2022-02-10T17:39:25.878Z"},"accession":"S-EPMC8220418","cross_references":{"pubmed":["34194673"],"doi":["10.1016/j.csbj.2021.06.006"]}}