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...
| Autores: | , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad del País Vasco |
| Repositorio: | Addi. Archivo Digital para la Docencia y la Investigación |
| OAI Identifier: | oai:addi.ehu.eus:10810/69453 |
| Acceso en línea: | http://hdl.handle.net/10810/69453 |
| Access Level: | acceso abierto |
| Palabra clave: | blood types Bombay blood type rare blood types glycoside hydrolases fucosidase enzyme specificity carbohydrate-active enzymes |
| Sumario: | 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 a novel 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. We provide high-resolution X-ray crystal structures of FucOB, which show a three-domain architecture, including a GH95 glycoside hydrolase. In combination with site-directed mutagenesis, enzymatic activity and computational methods we unveil the molecular basis of 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. |
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