8PXT

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

Summary for 8PXT

• Entry DOI: 10.2210/pdb8pxt/pdb
• Descriptor: Beta-N-acetylhexosaminidase, 2-acetamido-2-deoxy-beta-D-galactopyranose, SODIUM ION, ... (5 entities in total)
• Functional Keywords: beta-hexosaminidase, akkermansia muciniphila, galnac-b converting, cbm, hydrolase
• Biological source: Akkermansia muciniphila
• Total number of polymer chains: 3
• Total formula weight: 221428.80

Authors

Jensen, M.,Abou Hachem, M.,Morth, J.P. (deposition date: 2023-07-24, release date: 2024-02-28, Last modification date: 2024-05-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.25 Å)