A5075506500- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Galectins and Cancer Biology
- Machine Learning in Bioinformatics
- Enzyme Production and Characterization
- Lysosomal Storage Disorders Research
- Biochemical and Molecular Research
- Enzyme Catalysis and Immobilization
- RNA and protein synthesis mechanisms
Universitat de Barcelona
2020-2024
Instituto de Química Orgánica General
2023
α-Mannoside β-1,6-N-acetylglucosaminyltransferase V (MGAT5) is a mammalian glycosyltransferase involved in complex N-glycan formation, which strongly drives cancer when overexpressed. Despite intense interest, the catalytic mechanism of MGAT5 not known detail, precluding therapeutic exploitation. We solved structures complexed to glycosyl donor and acceptor ligands, revealing an unforeseen role for donor-induced loop rearrangements controlling substrate engagement. QM/MM metadynamics...
Retaining glycoside hydrolases use acid/base catalysis with an enzymatic protonating the glycosidic bond oxygen to facilitate leaving-group departure alongside attack by a catalytic nucleophile form covalent intermediate. Generally, this protonates laterally respect sugar ring, which places and carboxylates within about 4.5-6.5 Å of each other. However, in hydrolase (GH) family 116, including disease-related human acid β-glucosidase 2 (GBA2), distance between is around 8 (PDB: 5BVU) appears...
O-glycosylation is a post-translational protein modification essential to life. One of the enzymes involved in this process O-fucosyltransferase 1 (POFUT1), which fucosylates threonine or serine residues within specific sequence context epidermal growth factor-like domains (EGF-LD). Unlike most inverting glycosyltransferases, POFUT1 lacks basic residue active site that could act as catalytic base deprotonate Thr/Ser EGF-LD acceptor during chemical reaction. Using quantum mechanics/molecular...
Abstract In silico modelling of proteins comprises a diversity computational tools aimed to obtain structural, electronic, and/or dynamic information about these biomolecules, capturing mechanistic details that are challenging experimental approaches, such as elusive enzyme-substrate complexes, short-lived intermediates, and reaction transition states (TS). The present article gives the reader insight on use in techniques understand complex catalytic mechanisms carbohydrate-active enzymes...
Abstract Soluble HMW1C-like N -glycosyltransferases (NGTs) catalyze the glycosylation of Asn residues in proteins, a process fundamental for bacterial autoaggregation, adhesion and pathogenicity. However, our understanding their molecular mechanisms is hindered by lack structures enzymatic complexes. Here, we report binary ternary NGT complexes Aggregatibacter aphrophilus ( Aa NGT), revealing an essential dyad basic/acidic located N-terminal all α-domain (AAD) that intimately recognizes Thr...
Correct elaboration of N-linked glycans in the secretory pathway human cells is essential physiology. Early N-glycan biosynthesis follows an assembly line principle before undergoing crucial points that feature sequential incorporation sugar N-acetylglucosamine (GlcNAc). The activity GlcNAc transferase V (MGAT5) primes antenna heavily upregulated cancer. Yet, functional relevance and substrate choice MGAT5 are ill-defined. Here, we employ a tactic termed bump-and-hole engineering to develop...
Correct elaboration of N-linked glycans in the secretory pathway human cells is essential physiology. Early N-glycan biosynthesis follows an assembly line principle before undergoing crucial points that feature sequential incorporation sugar