6usa | pdb_00006usa

Crystal structure of tryptophan synthase from M. tuberculosis - aminoacrylate- and GSK1-bound form

spinqualitylabelsall models 6usa, resolution 2.41Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6usa is a 8 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, EDO, FMT, K, MLI, NA, P1T, PEG, PZJ, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [TRPA_MYCTU] The alpha subunit is responsible for the aldol cleavage of indoleglycerol phosphate to indole and glyceraldehyde 3-phosphate. Publication Abstract from PubMed Global dispersion of multidrug resistant bacteria is very common and evolution of antibiotic-resistance is occurring at an alarming rate, presenting a formidable challenge for humanity. The development of new therapeuthics with novel molecular targets is urgently needed. Current drugs primarily affect protein, nucleic acid, and cell wall synthesis. Metabolic pathways, including those involved in amino acid biosynthesis, have recently sparked interest in the drug discovery community as potential reservoirs of such novel targets. Tryptophan biosynthesis, utilized by bacteria but absent in humans, represents one of the currently studied processes with a therapeutic focus. It has been shown that tryptophan synthase (TrpAB) is required for survival of Mycobacterium tuberculosis in macrophages and for evading host defense, and therefore is a promising drug target. Here we present crystal structures of TrpAB with two allosteric inhibitors of M. tuberculosis tryptophan synthase that belong to sulfolane and indole-5-sulfonamide chemical scaffolds. We compare our results with previously reported structural and biochemical studies of another, azetidine-containing M. tuberculosis tryptophan synthase inhibitor. This work shows how structurally distinct ligands can occupy the same allosteric site and make specific interactions. It also highlights the potential benefit of targeting more variable allosteric sites of important metabolic enzymes. Allosteric inhibitors of Mycobacterium tuberculosis tryptophan synthase.,Michalska K, Chang C, Maltseva NI, Jedrzejczak R, Robertson GT, Gusovsky F, McCarren P, Schreiber SL, Nag PP, Joachimiak A Protein Sci. 2020 Mar;29(3):779-788. doi: 10.1002/pro.3825. Epub 2020 Jan 20. PMID:31930594 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tryptophan synthase 3D structures

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