8P0Q

Crystal structure of AaNGT complexed to UDP and a peptide

8P0Q の概要

• エントリーDOI: 10.2210/pdb8p0q/pdb
• 分子名称: Adhesin, PHE-GLY-ASN-TRP-THR-THR, URIDINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: n-glycosylation, asn tautomeric form, aad, glycosyltransferase, gt-b, transferase
• 由来する生物種: Aggregatibacter aphrophilus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 143877.19

構造登録者

Piniello, B.,Macias-Leon, J.,Rovira, C.,Hurtado-Guerrero, R. (登録日: 2023-05-10, 公開日: 2023-09-06, 最終更新日: 2023-09-27)

主引用文献

Piniello, B.,Macias-Leon, J.,Miyazaki, S.,Garcia-Garcia, A.,Companon, I.,Ghirardello, M.,Taleb, V.,Veloz, B.,Corzana, F.,Miyagawa, A.,Rovira, C.,Hurtado-Guerrero, R.
Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase.
Nat Commun, 14:5785-5785, 2023

PubMed Abstract: Soluble HMW1C-like N-glycosyltransferases (NGTs) catalyze the glycosylation of Asn residues in proteins, a process fundamental for bacterial autoaggregation, adhesion and pathogenicity. However, our understanding of their molecular mechanisms is hindered by the lack of structures of enzymatic complexes. Here, we report structures of binary and ternary NGT complexes of Aggregatibacter aphrophilus NGT (AaNGT), revealing an essential dyad of basic/acidic residues located in the N-terminal all α-domain (AAD) that intimately recognizes the Thr residue within the conserved motif Asn-X-Ser/Thr. Poor substrates and inhibitors such as UDP-galactose and UDP-glucose mimetics adopt non-productive conformations, decreasing or impeding catalysis. QM/MM simulations rationalize these results, showing that AaNGT follows a S2 reaction mechanism in which the acceptor asparagine uses its imidic form for catalysis and the UDP-glucose phosphate group acts as a general base. These findings provide key insights into the mechanism of NGTs and will facilitate the design of structure-based inhibitors to treat diseases caused by non-typeable H. influenzae or other Gram-negative bacteria.

PubMed: 37723184
DOI: 10.1038/s41467-023-41238-1

実験手法

X-RAY DIFFRACTION (2.8 Å)