title: Inhibition of microbial β-N-acetylhexosaminidases by 4-deoxy- and galacto-analogues of NAG-thiazoline.
abstract: NAG-thiazoline is a well-established competitive inhibitor of two physiologically relevant glycosidase families-β-N-acetylhexosaminidases (GH20) and β-N-acetylglucosaminidases (GH84). Based on the different substrate flexibilities of these enzyme groups, we designed and synthesized the 4-deoxy derivative of NAG-thiazoline aiming at the selective inhibition of GH20 β-N-acetylhexosaminidases. One GH84 and two GH20 microbial glycosidases were employed as model enzymes for the inhibition assays. Surprisingly, the new compound 4-deoxy-thiazoline exhibited no activity inhibition with either of the enzyme families of interest. Unlike with the substrates, the 4-hydroxyl group of the inhibitor's sugar ring seems to be crucial for binding the inhibitor to the active sites of these enzymes.
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ 14220 Praha 4, Czech Republic; Department of Biochemistry and Microbiology, Institute of Chemical Technology Prague, Technická 5, CZ 16628 Praha 6, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Krejzová
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ 14220 Praha 4, Czech Republic.
authors.forename: Lubica
authors.initials: L
authors.lastname: Kalachova
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ 14220 Praha 4, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Šimon
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ 14220 Praha 4, Czech Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Pelantová
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ 14220 Praha 4, Czech Republic. Electronic address: slamova@biomed.cas.cz.
authors.forename: Kristýna
authors.initials: K
authors.lastname: Slámová
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ 14220 Praha 4, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Křen
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001439:Bacteroides / Q000201:enzymology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005658:Fungi / Q000201:enzymology; D007700:Kinetics; D011485:Protein Binding; D013302:Streptomyces / Q000201:enzymology; D013379:Substrate Specificity; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D005656:Fungal Proteins; D013844:Thiazoles; D001619:beta-N-Acetylhexosaminidases; C487818:N-acetylglucosamine thiazoline; D000117:Acetylglucosamine
keywords: Enzyme inhibition; NAG-thiazoline; O-GlcNAcase; β-N-Acetylhexosaminidase