Evidence for substrate-assisted catalysis in N-acetylphosphoglucosamine mutase

Raimi, O.G. ; Hurtado-Guerrero, R. (Universidad de Zaragoza) ; Van Aalten, D.M.F.

Resumen: N-acetylphosphoglucosamine mutase (AGM1) is a key component of the hexosamine biosynthetic pathway that produces UDP-GlcNAc, an essential precursor for a wide range of glycans in eukaryotes. AGM belongs to the a-D-phosphohexomutase metalloenzyme superfamily and catalyzes the interconversion of N-acetylglucosamine-6-phosphate (GlcNAc-6P) to N-acetylglucosamine-1-phosphate (GlcNAc-1P) through N-acetylglucosa-mine-1, 6-bisphosphate (GlcNAc-1, 6-bisP) as the catalytic intermediate. Although there is an understanding of the phosphoserine-dependent catalytic mechanism at enzymatic and structural level, the identity of the requisite catalytic base in AGM1/phosphoglucomu-tases is as yet unknown. Here, we present crystal structures of a Michaelis complex of AGM1 with GlcNAc-6P and Mg2+, and a complex of the inactive Ser69Ala mutant together with glucose-1, 6-bisphosphate (Glc-1, 6-bisP) that represents key snapshots along the reaction co-ordinate. Together with mutagenesis, these structures reveal that the phosphate group of the hexose-1, 6-bisP intermediate may act as the catalytic base.

Idioma: Inglés

DOI: 10.1042/BCJ20180172

Año: 2018

Publicado en: BIOCHEMICAL JOURNAL 475, 15 (2018), 2547-2557
ISSN: 0264-6021

Factor impacto JCR: 4.331 (2018)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 72 / 294 = 0.245 (2018) - Q1 - T1

Factor impacto SCIMAGO: 2.142 - Biochemistry (Q1) - Molecular Biology (Q1) - Cell Biology (Q1)

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)