2CH6

Crystal structure of human N-acetylglucosamine kinase in complex with ADP and glucose

2CH6 の概要

• エントリーDOI: 10.2210/pdb2ch6/pdb
• 関連するPDBエントリー: 2CH5
• 分子名称: N-ACETYL-D-GLUCOSAMINE KINASE, ADENOSINE-5'-DIPHOSPHATE, alpha-D-glucopyranose (3 entities in total)
• 機能のキーワード: transferase, sugar kinase, ribonuclease h fold, sugar kinase/hsp70/actin superfamily
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 152099.86

構造登録者

Weihofen, W.A.,Berger, M.,Chen, H.,Saenger, W.,Hinderlich, S. (登録日: 2006-03-13, 公開日: 2006-09-18, 最終更新日: 2024-05-08)

主引用文献

Weihofen, W.A.,Berger, M.,Chen, H.,Saenger, W.,Hinderlich, S.
Structures of Human N-Acetylglucosamine Kinase in Two Complexes with N-Acetylglucosamine and with Adp/Glucose: Insights Into Substrate Specificity and Regulation.
J.Mol.Biol., 364:388-, 2006

PubMed Abstract: N-Acetylglucosamine (GlcNAc), a major component of complex carbohydrates, is synthesized de novo or salvaged from lysosomally degraded glycoconjugates and from nutritional sources. The salvage pathway requires that GlcNAc kinase converts GlcNAc to GlcNAc-6-phosphate, a component utilized in UDP-GlcNAc biosynthesis or energy metabolism. GlcNAc kinase belongs to the sugar kinase/Hsp70/actin superfamily that catalyze phosphoryl transfer from ATP to their respective substrates, and in most cases catalysis is associated with a large conformational change in which the N-terminal small and C-terminal large domains enclose the substrates. Here we report two crystal structures of homodimeric human GlcNAc kinase, one in complex with GlcNAc and the other in complex with ADP and glucose. The active site of GlcNAc kinase is located in a deep cleft between the two domains of the V-shaped monomer. The enzyme adopts a "closed" configuration in the GlcNAc-bound complex and GlcNAc interacts with residues of both domains. In addition, the N-acetyl methyl group contacts residues of the other monomer in the homodimer, a unique feature compared to other members of the sugar kinase/Hsp70/actin superfamily. This contrasts an "open" configuration in the ADP/glucose-bound structure, where glucose cannot form these interactions, explaining its low binding affinity for GlcNAc kinase. Our results support functional implications derived from apo crystal structures of GlcNAc kinases from Chromobacter violaceum and Porphyromonas gingivalis and show that Tyr205, which is phosphorylated in thrombin-activated platelets, lines the GlcNAc binding pocket. This suggests that phosphorylation of Tyr205 may modulate GlcNAc kinase activity and/or specificity.

PubMed: 17010375
DOI: 10.1016/J.JMB.2006.08.085

実験手法

X-RAY DIFFRACTION (2.72 Å)