How to Find a Fragment: Methods for Screening and Validation in Fragment-Based Drug Discovery.

Fragment-based drug discovery (FBDD) is a crucial strategy for developing new drugs that have been applied to diverse targets, from neglected infectious diseases to cancer. With at least seven drugs already launched to the market, this approach has gained interest in both academics and industry in the last 20 years. FBDD relies on screening small libraries with about 1000-2000 compounds of low molecular weight (about 300 Da) using several biophysical methods.

Crystal structures of the closed form of Mycobacterium tuberculosis dihydrofolate reductase in complex with dihydrofolate and antifolates.

Tuberculosis is a disease caused by Mycobacterium tuberculosis and is the leading cause of death from a single infectious pathogen, with a high prevalence in developing countries in Africa and Asia. There still is a need for the development or repurposing of novel therapies to combat this disease owing to the long-term nature of current therapies and because of the number of reported resistant strains. Here, structures of dihydrofolate reductase from M.

Structural Basis for the Interaction and Processing of β-Lactam Antibiotics by l,d-Transpeptidase 3 (Ldt) from Mycobacterium tuberculosis.

Targeting Mycobacterium tuberculosis peptidoglycans with β-lactam antibiotics represents a strategy to address increasing resistance to antitubercular drugs. β-Lactams inhibit peptidoglycan synthases such as l,d-transpeptidases, a group of carbapenem-sensitive enzymes that stabilize peptidoglycans through 3 → 3 cross-links. M.