2HW1

Crystal structure of human ketohexokinase complexed to different sugar molecules

Summary for 2HW1

• Entry DOI: 10.2210/pdb2hw1/pdb
• Related: 2HQQ
• Descriptor: Ketohexokinase, beta-D-fructofuranose, SULFATE ION, ... (6 entities in total)
• Functional Keywords: fructose kinase, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 33642.79

Authors

Trinh, C.H.,Asipu, A.,Bonthron, D.T.,Phillips, S.E.V. (deposition date: 2006-07-31, release date: 2007-07-10, Last modification date: 2023-08-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.1 Å)