6fxy | pdb_00006fxy

Crystal Structure of full-length Human Lysyl Hydroxylase LH3 - Cocrystal with Fe2+, Mn2+, UDP-Gal - Structure from long-wavelength S-SAD

spinqualitylabelsall models 6fxy, resolution 2.14Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6fxy is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: AKG, FE2, GOL, MN, NAG, UDP Activity: Oxidoreductase, with EC number 1.14.11.4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [PLOD3_HUMAN] Connective tissue disorder due to lysyl hydroxylase-3 deficiency. The disease is caused by mutations affecting the gene represented in this entry. Function [PLOD3_HUMAN] Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens. These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links.[UniProtKB:P24802] Publication Abstract from PubMed 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. Molecular architecture of the multifunctional collagen lysyl hydroxylase and glycosyltransferase LH3.,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 Nat Commun. 2018 Aug 8;9(1):3163. doi: 10.1038/s41467-018-05631-5. PMID:30089812 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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