4D6I

Crystal structure of a family 98 glycoside hydrolase catalytic module (Sp3GH98) in complex with the type 1 blood group A-tetrasaccharide (E558A L19 mutant)

Summary for 4D6I

• Entry DOI: 10.2210/pdb4d6i/pdb
• Related: 4D6C 4D6D 4D6E 4D6F 4D6G 4D6H 4D6J
• Descriptor: GLYCOSIDE HYDROLASE, alpha-L-fucopyranose-(1-2)-[2-acetamido-2-deoxy-alpha-D-galactopyranose-(1-3)]beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: hydrolase, blood group antigen
• Biological source: STREPTOCOCCUS PNEUMONIAE
• Total number of polymer chains: 1
• Total formula weight: 69867.36

Authors

Kwan, D.H.,Constantinescu, I.,Chapanian, R.,Higgins, M.A.,Samain, E.,Boraston, A.B.,Kizhakkedathu, J.N.,Withers, S.G. (deposition date: 2014-11-11, release date: 2014-11-26, Last modification date: 2023-12-20)

Primary citation

Kwan, D.H.,Constantinescu, I.,Chapanian, R.,Higgins, M.A.,Koetzler, M.,Samain, E.,Boraston, A.B.,Kizhakkedathu, J.N.,Withers, S.G.
Towards Efficient Enzymes for the Generation of Universal Blood Through Structure-Guided Directed Evolution.
J.Am.Chem.Soc., 137:5695-, 2015

PubMed Abstract: 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.

PubMed: 25870881
DOI: 10.1021/JA5116088

Experimental method

X-RAY DIFFRACTION (1.99 Å)