AI Article Synopsis

  • The L-arginine biosynthesis pathway has 8 enzymes that help turn a substance called L-glutamate into another good one called L-arginine.
  • Certain types of bacteria that can't make L-arginine can be easily killed in mice, and stopping an enzyme called ArgJ helps get rid of a long-lasting infection.
  • Researchers are looking at four of these enzymes to find new medicine to fight tuberculosis and have already found some promising candidates through various tests.

Article 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 are rapidly sterilised in mice, while inhibition of ArgJ with Pranlukast was found to clear chronic 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 confirmed to have on-target activity against . These results demonstrate the potential for more enzymes in this pathway to be targeted with dedicated drug discovery programmes.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220418PMC
http://dx.doi.org/10.1016/j.csbj.2021.06.006DOI Listing

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