1NQW

Crystal Structure of Lumazine Synthase from Aquifex aeolicus in Complex with Inhibitor: 5-(6-D-ribitylamino-2,4(1H,3H)pyrimidinedione-5-yl)-1-pentyl-phosphonic acid

1NQW の概要

• エントリーDOI: 10.2210/pdb1nqw/pdb
• 関連するPDBエントリー: 1NQU 1NQV 1NQX
• 分子名称: 6,7-dimethyl-8-ribityllumazine synthase, 5-(6-D-RIBITYLAMINO-2,4(1H,3H)PYRIMIDINEDIONE-5-YL) PENTYL-1-PHOSPHONIC ACID (3 entities in total)
• 機能のキーワード: lumazine synthase, aquifex aeolicus, inhibitor complex, vitamin biosynthesis, catalytic mechanism, transferase
• 由来する生物種: Aquifex aeolicus
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 85692.73

構造登録者

Zhang, X.,Meining, W.,Cushman, M.,Haase, I.,Fischer, M.,Bacher, A.,Ladenstein, R. (登録日: 2003-01-23, 公開日: 2004-01-23, 最終更新日: 2024-02-14)

主引用文献

Zhang, X.,Meining, W.,Cushman, M.,Haase, I.,Fischer, M.,Bacher, A.,Ladenstein, R.
A structure-based model of the reaction catalyzed by lumazine synthase from Aquifex aeolicus.
J.Mol.Biol., 328:167-182, 2003

PubMed Abstract: 6,7-Dimethyl-8-ribityllumazine is the biosynthetic precursor of riboflavin, which, as a coenzyme, plays a vital role in the electron transfer process for energy production in all cellular organisms. The enzymes involved in lumazine biosynthesis have been studied in considerable detail. However, the conclusive mechanism of the reaction catalyzed by lumazine synthase has remained unclear. Here, we report four crystal structures of the enzyme from the hyperthermophilic bacterium Aquifex aeolicus in complex with different inhibitor compounds. The structures were refined at resolutions of 1.72 A, 1.85 A, 2.05 A and 2.2 A, respectively. The inhibitors have been designed in order to mimic the substrate, the putative reaction intermediates and the final product. Structural comparisons of the native enzyme and the inhibitor complexes as well as the kinetic data of single-site mutants of lumazine synthase from Bacillus subtilis showed that several highly conserved residues at the active site, namely Phe22, His88, Arg127, Lys135 and Glu138 are most likely involved in catalysis. A structural model of the catalytic process, which illustrates binding of substrates, enantiomer specificity, proton abstraction/donation, inorganic phosphate elimination, formation of the Schiff base and cyclization is proposed.

PubMed: 12684006
DOI: 10.1016/S0022-2836(03)00186-4

実験手法

X-RAY DIFFRACTION (2.2 Å)