Bacterial glycosidases for the production of universal red blood cells
| Autor: | Jean Spence, Martin L. Olsson, Greg Pietz, Henrik Clausen, Kristen Saunders, Qiyong P Liu, Thayer White, Huaiping Yuan, Bernard Henrissat, Yves Bourne, John M. Neveu, Steven B. Levery, Edward Nudelman, Gerlind Sulzenbacher, Eric P. Bennett, William S. Lane |
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| Přispěvatelé: | Architecture et fonction des Macromolécules Biologiques - UMR 6098 (AFMB), Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Erythrocytes Glycoside Hydrolases [SDV]Life Sciences [q-bio] Molecular Sequence Data Biomedical Engineering Bioengineering Biology 01 natural sciences Applied Microbiology and Biotechnology Catalysis Protein Structure Secondary ABO Blood-Group System Substrate Specificity alpha-N-Acetylgalactosaminidase law.invention 03 medical and health sciences Antigen law ABO blood group system Internal medicine medicine Humans Glycoside hydrolase 030304 developmental biology chemistry.chemical_classification 0303 health sciences Binding Sites Hematology Bacteria 010405 organic chemistry Titrimetry Hydrogen-Ion Concentration Flow Cytometry 0104 chemical sciences 3. Good health Kinetics Red blood cell Enzyme medicine.anatomical_structure Blood Grouping and Crossmatching Prokaryotic Cells Biochemistry chemistry Recombinant DNA Molecular Medicine Chromatography Thin Layer NAD+ kinase Biotechnology |
| Zdroj: | Nature Biotechnology Nature Biotechnology, Nature Publishing Group, 2007, ⟨10.1038/nbt1298⟩ Nature Biotechnology, 2007, ⟨10.1038/nbt1298⟩ |
| ISSN: | 1546-1696 1087-0156 |
| DOI: | 10.1038/nbt1298 |
| Popis: | International audience; Enzymatic removal of blood group ABO antigens to develop universal red blood cells (RBCs) was a pioneering vision originally proposed more than 25 years ago. Although the feasibility of this approach was demonstrated in clinical trials for group B RBCs, a major obstacle in translating this technology to clinical practice has been the lack of efficient glycosidase enzymes. Here we report two bacterial glycosidase gene families that provide enzymes capable of efficient removal of A and B antigens at neutral pH with low consumption of recombinant enzymes. The crystal structure of a member of the aN -acetylgalactosaminidase family reveals an unusual catalytic mechanism involving NAD +. The enzymatic conversion processes we describe hold promise for achieving the goal of producing universal RBCs, which would improve the blood supply while enhancing the safety of clinical transfusions. |
| Databáze: | OpenAIRE |
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