Gmh5 – An Mnn10 Homologue in S. pombe N-Glycan Processing

The Schizosaccharomyces pombe Glycosyltransferase Gmh5 is a Functional Homologue of the α-1,6-Mannosyltransferase Mnn10 Crucial for N-Glycan Processing🔬
www.ftb.com.hr/archives/196...
#glycosyltransferase #mannosyltransferase #Schizosaccharomyces #CellWallIntegrity #DiamondOpenAccess #ftbjournal

#MPB
AmGT28/44 from Astragalus hit 100% conversion of pterocarpans to glucosides, scaling maackiain-3-O-G to 78 µg/mL.
Details: maxapress.com/article/doi/10.48130/mpb...
#Glycosyltransferase #NaturalProducts

Engineered cell cultures boost anti-inflammatory compounds in endangered snow lotus Researchers from the Qingdao Institute of Bioenergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences (CAS) have developed a novel method to enhance the production of valuable medi...

Engineered #cell_cultures boost #anti-inflammatory compounds in endangered #snow_lotus.

#bioengineering #syringin #glycosyltransferase #SiUGT72BZ2 #gene_expression

phys.org/news/2025-03...

Molecular Structure and Enzymatic Mechanism of the Human Collagen Hydroxylysine Galactosyltransferase GLT25D1/COLGALT1 During biosynthesis, collagen lysine residues undergo extensive post-translational modifications essential for the stability and functions of collagen supramolecular assemblies. In the endoplasmic reticulum, two distinct metal ion dependent enzyme families (i.e., multifunctional lysyl hydroxylases-glucosyltransferases LH/PLODs and galactosyltransferases GLT25D/COLGALT) alternatively operate on collagen lysine side chains ultimately generating the highly conserved α-(1,2)-glucosyl-β-(1,O)-galactosyl-5-hydroxylysine pattern. Malfunctions in the collagen lysine post-translational modification machinery is linked to multiple developmental pathologies as well as extracellular matrix alterations causing enhanced cellular proliferation and invasiveness of several solid tumors, prompting for an in-depth characterization of LH/PLOD and GLT25D/COLGALT enzyme families. Here, we present an integrative molecular study of GLT25D1/COLGALT, highlighting an elongated head-to-head homodimeric assembly characterized by an N-terminal segment of each monomer wrapping around its dimerization partner. Each monomer encompasses two Rossman fold-type domains (GT1 and GT2) separated by an extended linker. Both domains were found capable of binding Mn2+ cofactors and UDP-α-galactose donor substrates, resulting in four candidate catalytic sites per dimer. Site-directed mutagenesis and biochemical studies identify the C-terminal GT2 domain as the functional GLT25D1/COLGALT1 catalytic site, highlighting an unprecedented Glu-Asp-Asp motif critical for metal ion binding, and suggesting structural roles for the N-terminal GT1 essential for correct quaternary structure assembly. Conversely, dimerization was not a requirement for GLT25D1/COLGALT1 enzymatic activity in vitro , suggesting that the elongated enzyme homodimer assembly, resembling that of LH/PLOD binding partners, could represent a functional hallmark for correct recognition and successful processing of collagen lysine residues. ### Competing Interest Statement The authors have declared no competing interest.

Excited to share our new @biorxivpreprint describing the integrative molecular characterization of GLT25D1/COLGALT1, a #collagen #glycosyltransferase with many unusual features: www.biorxiv.org/content/10.1101/2024.06....

Identification of Regulatory Molecular “Hot Spots” for LH/PLOD Collagen Glycosyltransferase Activity 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.

New #publication! A summary of many years of work focusing on characterization of #collagen #lysylhydroxylase / #PLOD #glycosyltransferase activity. @AIRC_it @ArmeniseHarvard #mizutanifoundation #EUfunded @MSCActions @RegLombardia. Out now in @IJMS_MDPI. https://www.mdpi.com/1422-0067/24/13/11213#

Delighted to share our latest #publication, excellent collaboration with @drelisabradley @OSUWexMed describing PLOD1/LH1 variants implicated in Human Vascular Disease and new insights on PLOD1 as possible #collagen #glycosyltransferase https://doi.org/10.1016/j.trsl.2021.08.002 @DBB_UniPV @unipv