4D6C

Crystal structure of a family 98 glycoside hydrolase catalytic module (Sp3GH98)(L19 mutant)

4D6C の概要

• エントリーDOI: 10.2210/pdb4d6c/pdb
• 関連するPDBエントリー: 4D6D 4D6E 4D6F 4D6G 4D6H 4D6I 4D6J
• 分子名称: GLYCOSIDE HYDROLASE, 1,2-ETHANEDIOL (3 entities in total)
• 機能のキーワード: hydrolase, blood group antigen
• 由来する生物種: STREPTOCOCCUS PNEUMONIAE
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 69192.71

構造登録者

Kwan, D.H.,Constantinescu, I.,Chapanian, R.,Higgins, M.A.,Samain, E.,Boraston, A.B.,Kizhakkedathu, J.N.,Withers, S.G. (登録日: 2014-11-11, 公開日: 2014-11-26, 最終更新日: 2023-12-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.59 Å)