7UZ2

Structure of beta-glycosidase from Sulfolobus solfataricus in complex with C5a-fluoro-valienide.

7UZ2 の概要

• エントリーDOI: 10.2210/pdb7uz2/pdb
• 分子名称: Beta-galactosidase, (1R,2S,3R,4R)-5-fluoro-6-(hydroxymethyl)cyclohex-5-ene-1,2,3,4-tetrol (3 entities in total)
• 機能のキーワード: covalent inhibition, glycoside hydrolase, hydrolase
• 由来する生物種: Saccharolobus solfataricus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 114041.25

構造登録者

Danby, P.M.,Jeong, A.,Sim, L.,Sweeney, R.P.,Wardman, J.F.,Geissner, A.,Worrall, L.J.,Strynadka, N.C.J.,Withers, S.G. (登録日: 2022-05-08, 公開日: 2023-04-05, 最終更新日: 2024-10-16)

主引用文献

Danby, P.M.,Jeong, A.,Sim, L.,Sweeney, R.P.,Wardman, J.F.,Karimi, R.,Geissner, A.,Worrall, L.J.,Reid, J.P.,Strynadka, N.C.J.,Withers, S.G.
Vinyl Halide-Modified Unsaturated Cyclitols are Mechanism-Based Glycosidase Inhibitors.
Angew.Chem.Int.Ed.Engl., 62:e202301258-e202301258, 2023

PubMed Abstract: Suitably configured allyl ethers of unsaturated cyclitols act as substrates of β-glycosidases, reacting via allylic cation transition states. Incorporation of halogens at the vinylic position of these carbasugars, along with an activated leaving group, generates potent inactivators of β-glycosidases. Enzymatic turnover of these halogenated cyclitols (F, Cl, Br) displayed a counter-intuitive trend wherein the most electronegative substituents yielded the most labile pseudo-glycosidic linkages. Structures of complexes with the Sulfolobus β-glucosidase revealed similar enzyme-ligand interactions to those seen in complexes with a 2-fluorosugar inhibitor, the lone exception being displacement of tyrosine 322 from the active site by the halogen. Mutation of Y322 to Y322F largely abolished glycosidase activity, consistent with lost interactions at O5, but minimally affected (7-fold) rates of carbasugar hydrolysis, yielding a more selective enzyme for unsaturated cyclitol ether hydrolysis.

PubMed: 36940280
DOI: 10.1002/anie.202301258

実験手法

X-RAY DIFFRACTION (1.83 Å)