9EVK

Crystal Structure of human Collagen Hydroxylysine Galactosyltransferase GLT25D1/COLGALT1

9EVK の概要

• エントリーDOI: 10.2210/pdb9evk/pdb
• 分子名称: Procollagen galactosyltransferase 1, CHLORIDE ION, GALACTOSE-URIDINE-5'-DIPHOSPHATE, ... (7 entities in total)
• 機能のキーワード: collagen biosynthesis; extracellular matrix; post-translational modifications, glycosyltransferase, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 139017.27

構造登録者

De Marco, M.,Scietti, L.,Rai, S.R.,Mattoteia, D.,Pinnola, A.,Forneris, F. (登録日: 2024-03-30, 公開日: 2025-04-09, 最終更新日: 2025-04-23)

主引用文献

De Marco, M.,Rai, S.R.,Scietti, L.,Mattoteia, D.,Liberi, S.,Moroni, E.,Pinnola, A.,Vetrano, A.,Iacobucci, C.,Santambrogio, C.,Colombo, G.,Forneris, F.
Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1.
Nat Commun, 16:3624-3624, 2025

PubMed Abstract: During collagen biosynthesis, lysine residues undergo extensive post-translational modifications through the alternate action of two distinct metal ion-dependent enzyme families (i.e., LH/PLODs and GLT25D/COLGALT), ultimately producing the highly conserved α-(1,2)-glucosyl-β-(1,O)-galactosyl-5-hydroxylysine pattern. Malfunctions in these enzymes are linked to developmental pathologies and extracellular matrix alterations associated to enhanced aggressiveness of solid tumors. Here, we characterized human GLT25D1/COLGALT1, revealing an elongated head-to-head homodimeric assembly. Each monomer encompasses two domains (named GT1 and GT2), both unexpectedly capable of binding metal ion cofactors and UDP-α-galactose donor substrates, resulting in four candidate catalytic sites per dimer. We identify the catalytic site in GT2, featuring an unusual Glu-Asp-Asp motif critical for Mn binding, ruling out direct catalytic roles for the GT1 domain, but showing that in this domain the unexpectedly bound Ca and UDP-α-galactose cofactors are critical for folding stability. Dimerization, albeit not essential for GLT25D1/COLGALT1 activity, provides a critical molecular contact site for multi-enzyme assembly interactions with partner multifunctional LH/PLOD lysyl hydroxylase-glycosyltransferase enzymes.

PubMed: 40240392
DOI: 10.1038/s41467-025-59017-5

実験手法

X-RAY DIFFRACTION (3 Å)