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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Kim, JS; Chen, Z; Espinosa, Garcia, SA; Buhlheller, C; Zhang, B; Richards, SJ; Chen, T; Wu, J; Bruntz, RC; Gilliam, ME; Yamauchi, M; Liang, B; Guo, H.
Structural basis of collagen glucosyltransferase function and its serendipitous role in kojibiose synthesis.
Nat Commun. 2025; 16(1):6704 Doi: 10.1038/s41467-025-61973-x [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
Buhlheller Christoph
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Abstract:
Collagen glucosyltransferases catalyze collagen glucosylation critical for biology and diseases, yet their structural regulation remains unclear. Here, we report crystal structures of a mimiviral collagen glucosyltransferase in its apo form and in complexes with uridine diphosphate (UDP) and the disaccharide product. We reveal that the enzyme forms a homodimer, stabilized by a loop from one subunit locking into a cleft on the other, enabling UDP-glucose binding cooperativity and enzymatic activity, a property conserved in the human homolog. The structures support an induced fit model for UDP interaction. The dimerization also forms an extended cleft flanked by two active sites, likely facilitating collagen recognition. Unexpectedly, the mimiviral enzyme also synthesizes a prebiotic disaccharide kojibiose. An elongated pocket near the active site allows the enzyme to use UDP-glucose and glucose for kojibiose production. We confirm the enzyme's kojibiose synthesis activity in vitro and in vivo. These insights inform glucosyltransferase function and open new avenues for inhibitor development and kojibiose biosynthesis.
Find related publications in this database (using NLM MeSH Indexing)
Glucosyltransferases - metabolism, chemistry, genetics
Humans - administration & dosage
Collagen - metabolism, chemistry
Disaccharides - biosynthesis, metabolism
Crystallography, X-Ray - administration & dosage
Catalytic Domain - administration & dosage
Uridine Diphosphate - metabolism
Models, Molecular - administration & dosage
Uridine Diphosphate Glucose - metabolism
Glucose - metabolism
Protein Multimerization - administration & dosage

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