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PDBsum entry 4d6c
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References listed in PDB file
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Key reference
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Title
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Toward efficient enzymes for the generation of universal blood through structure-Guided directed evolution.
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Authors
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D.H.Kwan,
I.Constantinescu,
R.Chapanian,
M.A.Higgins,
M.P.Kötzler,
E.Samain,
A.B.Boraston,
J.N.Kizhakkedathu,
S.G.Withers.
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Ref.
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J Am Chem Soc, 2015,
137,
5695-5705.
[DOI no: ]
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PubMed id
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Abstract
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Blood transfusions are critically important in many medical procedures, but the
presence of antigens on red blood cells (RBCs, erythrocytes) means that careful
blood-typing must be carried out prior to transfusion to avoid adverse and
sometimes fatal reactions following transfusion. Enzymatic removal of the
terminal N-acetylgalactosamine or galactose of A- or B-antigens, respectively,
yields universal O-type blood, but is inefficient. Starting with the family 98
glycoside hydrolase from Streptococcus pneumoniae SP3-BS71 (Sp3GH98), which
cleaves the entire terminal trisaccharide antigenic determinants of both A- and
B-antigens from some of the linkages on RBC surface glycans, through several
rounds of evolution, we developed variants with vastly improved activity toward
some of the linkages that are resistant to cleavage by the wild-type enzyme. The
resulting enzyme effects more complete removal of blood group antigens from cell
surfaces, demonstrating the potential for engineering enzymes to generate
antigen-null blood from donors of various types.
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