6E06

Crystal structure of Mycobacterium tuberculosis dethiobiotin synthetase in complex with cytidine triphosphate solved by precipitant-ligand exchange (crystals grown in citrate precipitant)

6E06 の概要

• エントリーDOI: 10.2210/pdb6e06/pdb
• 関連するPDBエントリー: 3FGN 3FMF 3FMI 3FPA 4WOP 6CVE 6CVF 6CVU 6CVV 6CZB 6CZC 6CZD 6CZE 6E05
• 分子名称: ATP-dependent dethiobiotin synthetase BioD, CYTIDINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: enzyme, synthetase, nucleotide triphosphate binding, transferase
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 95925.50

構造登録者

Thompson, A.P.,Wegener, K.L.,Bruning, J.B.,Polyak, S.W. (登録日: 2018-07-06, 公開日: 2018-10-17, 最終更新日: 2023-10-11)

主引用文献

Thompson, A.P.,Wegener, K.L.,Booker, G.W.,Polyak, S.W.,Bruning, J.B.
Precipitant-ligand exchange technique reveals the ADP binding mode in Mycobacterium tuberculosis dethiobiotin synthetase.
Acta Crystallogr D Struct Biol, 74:965-972, 2018

PubMed Abstract: Dethiobiotin 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 Å resolution. This result demonstrates the utility of precipitant-ligand exchange, which may be widely applicable to protein crystallography.

PubMed: 30289406
DOI: 10.1107/S2059798318010136

実験手法

X-RAY DIFFRACTION (2.5 Å)