Turning universal O into rare Bombay type blood

Red blood cell antigens play critical roles in blood transfusion since donor incompatibilities can be lethal. Recipients with the rare total deficiency in H antigen, the Oh Bombay phenotype, can only be transfused with group Oh blood to avoid serious transfusion reactions. We discover FucOB from the...

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Detalhes bibliográficos
Autores: Anso, Itxaso, Naegeli, Andreas, Cifuente, Javier O., Orrantia, Ane, Andersson, Erica, Zenarruzabeitia, Olatz, Moraleda-Montoya, Alicia, García-Alija, Mikel, Corzana, Francisco, Orbe, Rafael A. Del, Borrego, Francisco, Trastoy, Beatriz, Sjögren, Jonathan, Guerin, Marcelo E.
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2023
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/377731
Acesso em linha:http://hdl.handle.net/10261/377731
Access Level:Acceso aberto
Palavra-chave:Bacteria
Enzymes
Glycobiology
X-ray crystallography
Descrição
Resumo:Red blood cell antigens play critical roles in blood transfusion since donor incompatibilities can be lethal. Recipients with the rare total deficiency in H antigen, the Oh Bombay phenotype, can only be transfused with group Oh blood to avoid serious transfusion reactions. We discover FucOB from the mucin-degrading bacteria Akkermansia muciniphila as an α-1,2-fucosidase able to hydrolyze Type I, Type II, Type III and Type V H antigens to obtain the afucosylated Bombay phenotype in vitro. X-ray crystal structures of FucOB show a three-domain architecture, including a GH95 glycoside hydrolase. The structural data together with site-directed mutagenesis, enzymatic activity and computational methods provide molecular insights into substrate specificity and catalysis. Furthermore, using agglutination tests and flow cytometry-based techniques, we demonstrate the ability of FucOB to convert universal O type into rare Bombay type blood, providing exciting possibilities to facilitate transfusion in recipients/patients with Bombay phenotype.