| http://purl.uniprot.org/citations/37446392 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/37446392 | http://www.w3.org/2000/01/rdf-schema#comment | "Hydroxylysine glycosylations are post-translational modifications (PTMs) essential for the maturation and homeostasis of fibrillar and non-fibrillar collagen molecules. The multifunctional collagen lysyl hydroxylase 3 (LH3/PLOD3) and the collagen galactosyltransferase GLT25D1 are the human enzymes that have been identified as being responsible for the glycosylation of collagen lysines, although a precise description of the contribution of each enzyme to these essential PTMs has not yet been provided in the literature. LH3/PLOD3 is thought to be capable of performing two chemically distinct collagen glycosyltransferase reactions using the same catalytic site: an inverting beta-1,O-galactosylation of hydroxylysines (Gal-T) and a retaining alpha-1,2-glucosylation of galactosyl hydroxylysines (Glc-T). In this work, we have combined indirect luminescence-based assays with direct mass spectrometry-based assays and molecular structure studies to demonstrate that LH3/PLOD3 only has Glc-T activity and that GLT25D1 only has Gal-T activity. Structure-guided mutagenesis confirmed that the Glc-T activity is defined by key residues in the first-shell environment of the glycosyltransferase catalytic site as well as by long-range contributions from residues within the same glycosyltransferase (GT) domain. By solving the molecular structures and characterizing the interactions and solving the molecular structures of human LH3/PLOD3 in complex with different UDP-sugar analogs, we show how these studies could provide insights for LH3/PLOD3 glycosyltransferase inhibitor development. Collectively, our data provide new tools for the direct investigation of collagen hydroxylysine PTMs and a comprehensive overview of the complex network of shapes, charges, and interactions that enable LH3/PLOD3 glycosyltransferase activities, expanding the molecular framework and facilitating an improved understanding and manipulation of glycosyltransferase functions in biomedical applications."xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.org/dc/terms/identifier | "doi:10.3390/ijms241311213"xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/author | "Roscioli T."xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/author | "Scietti L."xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/author | "Fumagalli M."xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/author | "Pinnola A."xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/author | "Forneris F."xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/author | "Chiapparino A."xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/author | "De Giorgi F."xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/author | "Faravelli S."xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/author | "De Marco M."xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/author | "Mattoteia D."xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/author | "Negro L."xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/name | "Int J Mol Sci"xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/pages | "11213"xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/title | "Identification of Regulatory Molecular "Hot Spots" for LH/PLOD Collagen Glycosyltransferase Activity."xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://purl.uniprot.org/core/volume | "24"xsd:string |
| http://purl.uniprot.org/citations/37446392 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/37446392 |
| http://purl.uniprot.org/citations/37446392 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/37446392 |
| http://purl.uniprot.org/uniprot/#_O60568-mappedCitation-37446392 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37446392 |
| http://purl.uniprot.org/uniprot/O60568 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/37446392 |