6e05
From Proteopedia
Crystal structure of Mycobacterium tuberculosis dethiobiotin synthetase in complex with cytidine triphosphate solved by precipitant-ligand exchange (crystals grown in sulfate precipitant)
Structural highlights
FunctionBIOD_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.[1] Publication Abstract from PubMedDethiobiotin synthetase from Mycobacterium tuberculosis (MtDTBS) is a promising antituberculosis drug target. Small-molecule inhibitors that target MtDTBS provide a route towards new therapeutics for the treatment of antibiotic-resistant tuberculosis. Adenosine diphosphate (ADP) is an inhibitor of MtDTBS; however, structural studies into its mechanism of inhibition have been unsuccessful owing to competitive binding to the enzyme by crystallographic precipitants such as citrate and sulfate. Here, a crystallographic technique termed precipitant-ligand exchange has been developed to exchange protein-bound precipitants with ligands of interest. Proof of concept for the exchange method was demonstrated using cytidine triphosphate (CTP), which adopted the same binding mechanism as that obtained with traditional crystal-soaking techniques. Precipitant-ligand exchange also yielded the previously intractable structure of MtDTBS in complex with ADP solved to 2.4 A resolution. This result demonstrates the utility of precipitant-ligand exchange, which may be widely applicable to protein crystallography. Precipitant-ligand exchange technique reveals the ADP binding mode in Mycobacterium tuberculosis dethiobiotin synthetase.,Thompson AP, Wegener KL, Booker GW, Polyak SW, Bruning JB Acta Crystallogr D Struct Biol. 2018 Oct 1;74(Pt 10):965-972. doi:, 10.1107/S2059798318010136. Epub 2018 Oct 2. PMID:30289406[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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