1LIO

STRUCTURE OF APO T. GONDII ADENOSINE KINASE

「1DH2」から置き換えられました

1LIO の概要

• エントリーDOI: 10.2210/pdb1lio/pdb
• 関連するPDBエントリー: 1LII 1LIJ 1LIK
• 分子名称: adenosine kinase (2 entities in total)
• 機能のキーワード: alpha-beta structure, transferase
• 由来する生物種: Toxoplasma gondii
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38364.73

構造登録者

Schumacher, M.A.,Scott, D.M.,Mathews, I.I.,Ealick, S.E.,Brennan, R.G. (登録日: 2002-04-17, 公開日: 2002-06-12, 最終更新日: 2024-02-14)

主引用文献

Schumacher, M.A.,Scott, D.M.,Mathews, I.I.,Ealick, S.E.,Roos, D.S.,Ullman, B.,Brennan, R.G.
Crystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding.
J.Mol.Biol., 298:875-893, 2000

PubMed Abstract: Adenosine kinase (AK) is a key purine metabolic enzyme from the opportunistic parasitic protozoan Toxoplasma gondii and belongs to the family of carbohydrate kinases that includes ribokinase. To understand the catalytic mechanism of AK, we determined the structures of the T. gondii apo AK, AK:adenosine complex and the AK:adenosine:AMP-PCP complex to 2.55 A, 2.50 A and 1.71 A resolution, respectively. These structures reveal a novel catalytic mechanism that involves an adenosine-induced domain rotation of 30 degrees and a newly described anion hole (DTXGAGD), requiring a helix-to-coil conformational change that is induced by ATP binding. Nucleotide binding also evokes a coil-to-helix transition that completes the formation of the ATP binding pocket. A conserved dipeptide, Gly68-Gly69, which is located at the bottom of the adenosine-binding site, functions as the switch for domain rotation. The synergistic structural changes that occur upon substrate binding sequester the adenosine and the ATP gamma phosphate from solvent and optimally position the substrates for catalysis. Finally, the 1.84 A resolution structure of an AK:7-iodotubercidin:AMP-PCP complex reveals the basis for the higher affinity binding of this prodrug over adenosine and thus provides a scaffold for the design of new inhibitors and subversive substrates that target the T. gondii AK.

PubMed: 10801355
DOI: 10.1006/jmbi.2000.3753

実験手法

X-RAY DIFFRACTION (2.5 Å)