7jt5

Mycobacterium tuberculosis dethiobiotin synthetase in complex with fragment analogue 9Mycobacterium tuberculosis dethiobiotin synthetase in complex with fragment analogue 9

Structural highlights 7jt5 is a 4 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. Method: X-ray diffraction, Resolution 2Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BIOD_MYCTU Catalyzes a mechanistically unusual reaction, the ATP-dependent insertion of CO2 between the N7 and N8 nitrogen atoms of 7,8-diaminopelargonic acid (DAPA) to form an ureido ring. Publication Abstract from PubMed Mycobacterium tuberculosis dethiobiotin synthase (MtDTBS) is a crucial enzyme involved in the biosynthesis of biotin in the causative agent of tuberculosis, M. tuberculosis. Here, we report a binder of MtDTBS, cyclopentylacetic acid 2 (KD = 3.4 +/- 0.4 mM), identified via in silico screening. X-ray crystallography showed that 2 binds in the 7,8-diaminopelargonic acid (DAPA) pocket of MtDTBS. Appending an acidic group to the para-position of the aromatic ring of the scaffold revealed compounds 4c and 4d as more potent binders, with KD = 19 +/- 5 and 17 +/- 1 muM, respectively. Further optimization identified tetrazole 7a as a particularly potent binder (KD = 57 +/- 5 nM) and inhibitor (Ki = 5 +/- 1 muM) of MtDTBS. Our findings highlight the first reported inhibitors of MtDTBS and serve as a platform for the further development of potent inhibitors and novel therapeutics for the treatment of tuberculosis. Inhibition of Mycobacterium tuberculosis Dethiobiotin Synthase (MtDTBS): Toward Next-Generation Antituberculosis Agents.,Schumann NC, Lee KJ, Thompson AP, Salaemae W, Pederick JL, Avery T, Gaiser BI, Hodgkinson-Bean J, Booker GW, Polyak SW, Bruning JB, Wegener KL, Abell AD ACS Chem Biol. 2021 Sep 17. doi: 10.1021/acschembio.1c00491. PMID:34533923 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dethiobiotin synthetase 3D structures

spinqualitylabelsall models 7jt5, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image