8PXT

Targeting extended blood antigens by Akkermansia muciniphila enzymes unveils a missing link for generating universal donor blood

8PXT の概要

• エントリーDOI: 10.2210/pdb8pxt/pdb
• 分子名称: Beta-N-acetylhexosaminidase, 2-acetamido-2-deoxy-beta-D-galactopyranose, SODIUM ION, ... (5 entities in total)
• 機能のキーワード: beta-hexosaminidase, akkermansia muciniphila, galnac-b converting, cbm, hydrolase
• 由来する生物種: Akkermansia muciniphila
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 221428.80

構造登録者

Jensen, M.,Abou Hachem, M.,Morth, J.P. (登録日: 2023-07-24, 公開日: 2024-02-28, 最終更新日: 2024-05-22)

主引用文献

Jensen, M.,Stenfelt, L.,Ricci Hagman, J.,Pichler, M.J.,Weikum, J.,Nielsen, T.S.,Hult, A.,Morth, J.P.,Olsson, M.L.,Abou Hachem, M.
Akkermansia muciniphila exoglycosidases target extended blood group antigens to generate ABO-universal blood.
Nat Microbiol, 9:1176-1188, 2024

PubMed Abstract: Matching donor and recipient blood groups based on red blood cell (RBC) surface ABO glycans and antibodies in plasma is crucial to avoid potentially fatal reactions during transfusions. Enzymatic conversion of RBC glycans to the universal group O is an attractive solution to simplify blood logistics and prevent ABO-mismatched transfusions. The gut symbiont Akkermansia muciniphila can degrade mucin O-glycans including ABO epitopes. Here we biochemically evaluated 23 Akkermansia glycosyl hydrolases and identified exoglycosidase combinations which efficiently transformed both A and B antigens and four of their carbohydrate extensions. Enzymatic removal of canonical and extended ABO antigens on RBCs significantly improved compatibility with group O plasmas, compared to conversion of A or B antigens alone. Finally, structural analyses of two B-converting enzymes identified a previously unknown putative carbohydrate-binding module. This study demonstrates the potential utility of mucin-degrading gut bacteria as valuable sources of enzymes for production of universal blood for transfusions.

PubMed: 38684911
DOI: 10.1038/s41564-024-01663-4

実験手法

X-RAY DIFFRACTION (2.25 Å)