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Glycoside Hydrolase Family 188

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Glycoside Hydrolase Family GH188
Clan GH-x
Mechanism NAD-dependent hydrolysis
Active site residues known
CAZy DB link

Substrate specificities

The glycoside hydrolases of this family are found in bacteria, algae, plants and a small number of archaea [1]. The family contains enzymes with sulfoquinovosidase activity (EC, namely the ability to cleave glycosides of 6-deoxy-6-sulfoquinovose. Sulfoquinovosidases are also found in family GH31 [2]. Enzymes of this family have the ability to cleave both α- and β-glycosides, and are dependent on an NAD+ cofactor. Sulfoquinovosidases hydrolyse glycosides of sulfoquinovose such as sulfoquinovosyl glycerol, and liberate free sulfoquinovose, which can be used as a substrate in bacterial sulfoglycolysis and sulfoquinovose sulfolysis pathways [3].

Kinetics and Mechanism

GH188 enzymes utilize an NAD-dependent hydrolysis mechanism that proceeds through oxidation-elimination-addition-reduction steps. Exchange of the substrate C2 proton with solvent deuterium during the enzyme-catalyzed reaction was demonstrated by mass spectrometry [1]. The following chemical mechanism is proposed: (1) C3 hydride abstraction via the reduction of NAD+ cofactor to NADH and simultaneous oxidation of the C3 hydroxyl group; (2) α to the ketone functionality, the C2 proton is deprotonated by a general catalytic base residue; (3) cleavage of the C1-O1 bond occurs in an α,β-elimination, producing an α,β-unsaturated ketone intermediate; (4) 1,4-Michael-like addition of a water molecule at C1; and (5) reduction of the C3 carbonyl functionality by the enzyme-bound NADH generates the product. Similar mechanisms are used in families GH4, GH109, GH177, and GH179.

Catalytic Residues

Catalytic residues can be inferred on the basis of X-ray crystallographic data for complexes of GH188 enzymes with NAD+ and sulfoquinovose [1]. Tyr136 in Arthrobacter sp. strain U41 SqgA is conserved in most family GH188 members and is located close to C2-OH, suggesting a possible role as a general base. His321 is located close to the C1-OH and may act as general acid (along with Tyr136) for the glycosidic oxygen facilitating glycosidic bond scission. The sulfonate group is recognized by a triad of amino acids: one oxygen H-bonds to Arg166 (2.6 Å), a second to Lys172 (2.9 Å), and a third to the backbone amide of Leu170 (2.8 Å).

Three-dimensional structures

Crystallographic data is available for at least two GH188 enzymes, including as complexes with NADH, and NADH plus sulfoquinovose. The 3D X-ray crystal structures include those of Flavobacterium sp. strain K172 SqgA (PDB 8QC8, 8QC2) and Arthrobacter sp. strain U41 SqgA (PDB 8QC3, 8QC6, 8QC5) [1]. Each enzyme possesses an N-terminal dinucleotide-binding Rossman fold. The GH188 enzymes show structural similarities to inositol-2-dehydrogenase, glucose-fructose/IDH/MocA-like oxidoreductase, and NAD+-dependent N-acetylgalactosaminidase of family GH109.

Family Firsts

First stereochemistry determination
not applicable
First catalytic residue identification
Arthrobacter sp. strain U41 SqgA using 3D X-ray crystal structure [1]
First 3-D structural determination
Flavobacterium sp. strain K172 SqgA and Arthrobacter sp. strain U41 SqgA [1]
First GH188 enzyme shown to hydrolyze both α- and β-substrates
Flavobacterium sp. strain K172 SqgA [1]


  1. Kaur A, Pickles IB, Sharma M, Madeido Soler N, Scott NE, Pidot SJ, Goddard-Borger ED, Davies GJ, and Williams SJ. (2023). Widespread Family of NAD(+)-Dependent Sulfoquinovosidases at the Gateway to Sulfoquinovose Catabolism. J Am Chem Soc. 2023;145(51):28216-28223. DOI:10.1021/jacs.3c11126 | PubMed ID:38100472 [Kaur2024]
  2. Speciale G, Jin Y, Davies GJ, Williams SJ, and Goddard-Borger ED. (2016). YihQ is a sulfoquinovosidase that cleaves sulfoquinovosyl diacylglyceride sulfolipids. Nat Chem Biol. 2016;12(4):215-7. DOI:10.1038/nchembio.2023 | PubMed ID:26878550 [Speciale2016]
  3. Snow AJD, Burchill L, Sharma M, Davies GJ, and Williams SJ. (2021). Sulfoglycolysis: catabolic pathways for metabolism of sulfoquinovose. Chem Soc Rev. 2021;50(24):13628-13645. DOI:10.1039/d1cs00846c | PubMed ID:34816844 [Snow2021]

All Medline abstracts: PubMed