4AIS

A complex structure of BtGH84

4AIS の概要

• エントリーDOI: 10.2210/pdb4ais/pdb
• 関連するPDBエントリー: 2CHN 2CHO 2J47 2J4G 2JIW 2VVN 2VVS 2W4X 2W66 2W67 2WCA 2WZH 2WZI 2X0H 2XJ7 2XM1 2XM2 4AIU
• 分子名称: O-GLCNACASE BT_4395, GLYCOLIC ACID, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: hydrolase, inhibitor
• 由来する生物種: BACTEROIDES THETAIOTAOMICRON VPI-5482
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 169604.23

構造登録者

He, Y.,Davies, G.J. (登録日: 2012-02-13, 公開日: 2012-06-20, 最終更新日: 2023-12-20)

主引用文献

Macauley, M.S.,Chan, J.,Zandberg, W.F.,He, Y.,Whitworth, G.E.,Stubbs, K.A.,Yuzwa, S.A.,Bennet, A.J.,Varki, A.,Davies, G.J.,Vocadlo, D.J.
Metabolism of Vertebrate Amino Sugars with N-Glycolyl Groups: Intracellular Beta-O-Linked N-Glycolylglucosamine (Glcngc), Udp-Glcngc, and the Biochemical and Structural Rationale for the Substrate Tolerance of Beta-O-Linked Beta-N-Acetylglucosaminidase.
J.Biol.Chem., 287:28882-, 2012

PubMed Abstract: The O-GlcNAc modification involves the attachment of single β-O-linked N-acetylglucosamine residues to serine and threonine residues of nucleocytoplasmic proteins. Interestingly, previous biochemical and structural studies have shown that O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc from proteins, has an active site pocket that tolerates various N-acyl groups in addition to the N-acetyl group of GlcNAc. The remarkable sequence and structural conservation of residues comprising this pocket suggest functional importance. We hypothesized this pocket enables processing of metabolic variants of O-GlcNAc that could be formed due to inaccuracy within the metabolic machinery of the hexosamine biosynthetic pathway. In the accompanying paper (Bergfeld, A. K., Pearce, O. M., Diaz, S. L., Pham, T., and Varki, A. (2012) J. Biol. Chem. 287, 28865-28881), N-glycolylglucosamine (GlcNGc) was shown to be a catabolite of NeuNGc. Here, we show that the hexosamine salvage pathway can convert GlcNGc to UDP-GlcNGc, which is then used to modify proteins with O-GlcNGc. The kinetics of incorporation and removal of O-GlcNGc in cells occur in a dynamic manner on a time frame similar to that of O-GlcNAc. Enzymatic activity of O-GlcNAcase (OGA) toward a GlcNGc glycoside reveals OGA can process glycolyl-containing substrates fairly efficiently. A bacterial homolog (BtGH84) of OGA, from a human gut symbiont, also processes O-GlcNGc substrates, and the structure of this enzyme bound to a GlcNGc-derived species reveals the molecular basis for tolerance and binding of GlcNGc. Together, these results demonstrate that analogs of GlcNAc, such as GlcNGc, are metabolically viable species and that the conserved active site pocket of OGA likely evolved to enable processing of mis-incorporated analogs of O-GlcNAc and thereby prevent their accumulation. Such plasticity in carbohydrate processing enzymes may be a general feature arising from inaccuracy in hexosamine metabolic pathways.

PubMed: 22692202
DOI: 10.1074/JBC.M112.363721

実験手法

X-RAY DIFFRACTION (2 Å)