2HW1

Crystal structure of human ketohexokinase complexed to different sugar molecules

2HW1 の概要

• エントリーDOI: 10.2210/pdb2hw1/pdb
• 関連するPDBエントリー: 2HQQ
• 分子名称: Ketohexokinase, beta-D-fructofuranose, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: fructose kinase, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33642.79

構造登録者

Trinh, C.H.,Asipu, A.,Bonthron, D.T.,Phillips, S.E.V. (登録日: 2006-07-31, 公開日: 2007-07-10, 最終更新日: 2023-08-30)

主引用文献

Trinh, C.H.,Asipu, A.,Bonthron, D.T.,Phillips, S.E.
Structures of alternatively spliced isoforms of human ketohexokinase.
Acta Crystallogr.,Sect.D, 65:201-211, 2009

PubMed Abstract: A molecular understanding of the unique aspects of dietary fructose metabolism may be the key to understanding and controlling the current epidemic of fructose-related obesity, diabetes and related adverse metabolic states in Western populations. Fructose catabolism is initiated by its phosphorylation to fructose 1-phosphate, which is performed by ketohexokinase (KHK). Here, the crystal structures of the two alternatively spliced isoforms of human ketohexokinase, hepatic KHK-C and the peripheral isoform KHK-A, and of the ternary complex of KHK-A with the substrate fructose and AMP-PNP are reported. The structure of the KHK-A ternary complex revealed an active site with both the substrate fructose and the ATP analogue in positions ready for phosphorylation following a reaction mechanism similar to that of the pfkB family of carbohydrate kinases. Hepatic KHK deficiency causes the benign disorder essential fructosuria. The effects of the disease-causing mutations (Gly40Arg and Ala43Thr) have been modelled in the context of the KHK structure.

PubMed: 19237742
DOI: 10.1107/S0907444908041115

実験手法

X-RAY DIFFRACTION (2.1 Å)