6FXK
Crystal Structure of full-length Human Lysyl Hydroxylase LH3
Summary for 6FXK
| Entry DOI | 10.2210/pdb6fxk/pdb |
| Descriptor | Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, GLYCEROL, ... (6 entities in total) |
| Functional Keywords | lysyl hydroxylase, galacosyltransferase, glucosyltransferase, collagen, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 83816.15 |
| Authors | Scietti, L.,Chiapparino, A.,De Giorgi, F.,Fumagalli, M.,Khoriauli, L.,Nergadze, S.,Basu, S.,Olieric, V.,Banushi, B.,Giulotto, E.,Gissen, P.,Forneris, F. (deposition date: 2018-03-09, release date: 2018-08-22, Last modification date: 2024-10-09) |
| Primary citation | Scietti, L.,Chiapparino, A.,De Giorgi, F.,Fumagalli, M.,Khoriauli, L.,Nergadze, S.,Basu, S.,Olieric, V.,Cucca, L.,Banushi, B.,Profumo, A.,Giulotto, E.,Gissen, P.,Forneris, F. Molecular architecture of the multifunctional collagen lysyl hydroxylase and glycosyltransferase LH3. Nat Commun, 9:3163-3163, 2018 Cited by PubMed Abstract: Lysyl hydroxylases catalyze hydroxylation of collagen lysines, and sustain essential roles in extracellular matrix (ECM) maturation and remodeling. Malfunctions in these enzymes cause severe connective tissue disorders. Human lysyl hydroxylase 3 (LH3/PLOD3) bears multiple enzymatic activities, as it catalyzes collagen lysine hydroxylation and also their subsequent glycosylation. Our understanding of LH3 functions is currently hampered by lack of molecular structure information. Here, we present high resolution crystal structures of full-length human LH3 in complex with cofactors and donor substrates. The elongated homodimeric LH3 architecture shows two distinct catalytic sites at the N- and C-terminal boundaries of each monomer, separated by an accessory domain. The glycosyltransferase domain displays distinguishing features compared to other known glycosyltransferases. Known disease-related mutations map in close proximity to the catalytic sites. Collectively, our results provide a structural framework characterizing the multiple functions of LH3, and the molecular mechanisms of collagen-related diseases involving human lysyl hydroxylases. PubMed: 30089812DOI: 10.1038/s41467-018-05631-5 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
Download full validation report
