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2hw1
From Proteopedia
| 2hw1, resolution 2.10Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Sites: | , , and | ||||||||
| Ligands: | , , , | ||||||||
| Gene: | KHK (Homo sapiens) | ||||||||
| Activity: | Ketohexokinase, with EC number 2.7.1.3 | ||||||||
| Related: | 2hqq | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Crystal structure of human ketohexokinase complexed to different sugar molecules
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.
Structures of alternatively spliced isoforms of human ketohexokinase., Trinh CH, Asipu A, Bonthron DT, Phillips SE, Acta Crystallogr D Biol Crystallogr. 2009 Mar;65(Pt 3):201-11. Epub 2009, Feb 20. PMID:19237742
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2HW1 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Trinh CH, Asipu A, Bonthron DT, Phillips SE. Structures of alternatively spliced isoforms of human ketohexokinase. Acta Crystallogr D Biol Crystallogr. 2009 Mar;65(Pt 3):201-11. Epub 2009, Feb 20. PMID:19237742 doi:S0907444908041115
Page seeded by OCA on Wed Sep 22 11:30:55 2010
