4AZC

Differential inhibition of the tandem GH20 catalytic modules in the pneumococcal exo-beta-D-N-acetylglucosaminidase, StrH

4AZC の概要

• エントリーDOI: 10.2210/pdb4azc/pdb
• 関連するPDBエントリー: 2YL5 2YL6 2YL8 2YL9 2YLA 2YLL 4AZ5 4AZ6 4AZ7 4AZB 4AZG 4AZH 4AZI
• 分子名称: BETA-N-ACETYLHEXOSAMINIDASE, (2S,3aR,5R,6S,7R,7aR)-5-(hydroxymethyl)-2-methyl-2,3a,5,6,7,7a-hexahydro-1H-pyrano[3,2-d][1,3]thiazole-6,7-diol, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: STREPTOCOCCUS PNEUMONIAE; 詳細
• 細胞内の位置: Secreted, cell wall; Peptidoglycan-anchor (Potential): P49610 P49610
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 199878.78

構造登録者

Pluvinage, B.,Stubbs, K.A.,Vocadlo, D.J.,Boraston, A.B. (登録日: 2012-06-25, 公開日: 2013-07-10, 最終更新日: 2023-12-20)

主引用文献

Pluvinage, B.,Stubbs, K.A.,Vocadlo, D.J.,Boraston, A.B.
Inhibition of the Family 20 Glycoside Hydrolase Catalytic Modules in the Streptococcus Pneumoniae Exo-Beta-D-N-Acetylglucosaminidase, Strh.
Org.Biomol.Chem., 11:7907-, 2013

PubMed Abstract: Streptococcus pneumoniae produces a cell-surface attached β-N-acetylglucosaminidase called StrH that is used by this pathogen to process the termini of host complex N-linked glycans. N-Acetyl-D-glucosamine-thiazoline (NAG-Thiazoline, NGT) and O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) are inhibitors of the two family 20 glycoside hydrolase catalytic modules within StrH and these inhibitors have proven useful in modulating the activity of StrH in assays that model aspects of the host-bacterium interaction. Here we explore the molecular basis of StrH inhibition through structural, kinetic, thermodynamic and site-directed mutagenic analyses using the recombinantly produced independent catalytic modules of StrH (GH20A and GH20B) and the inhibitors NGT and PUGNAc. The results reveal a similar binding mode of the sugar moiety of these inhibitors at the -1 subsite in the active sites of GH20A and GH20B. The lower affinity of NGT as compared to PUGNAc for these catalytic modules can be attributed to the hydrophobic phenylcarbamate moiety of PUGNAc that is absent in NGT. This moiety also displayed variations in its interactions with the active sites of GH20A and GH20B that provide a rationale for the 400-fold difference observed in the Ki values of this compound for these two β-N-acetylglucosaminidase catalytic modules.

PubMed: 24132305
DOI: 10.1039/C3OB41579A

実験手法

X-RAY DIFFRACTION (2.09 Å)