Patenaude Sonia I, Seto Nina O L, Borisova Svetlana N, Szpacenko Adam, Marcus Sandra L, Palcic Monica M, Evans Stephen V
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, K1H 8M5 Canada.
Nat Struct Biol. 2002 Sep;9(9):685-90. doi: 10.1038/nsb832.
The human ABO(H) blood group antigens are produced by specific glycosyltransferase enzymes. An N-acetylgalactosaminyltransferase (GTA) uses a UDP-GalNAc donor to convert the H-antigen acceptor to the A antigen, whereas a galactosyltransferase (GTB) uses a UDP-galactose donor to convert the H-antigen acceptor to the B antigen. GTA and GTB differ only in the identity of four critical amino acid residues. Crystal structures at 1.8-1.32 A resolution of the GTA and GTB enzymes both free and in complex with disaccharide H-antigen acceptor and UDP reveal the basis for donor and acceptor specificity and show that only two of the critical amino acid residues are positioned to contact donor or acceptor substrates. Given the need for stringent stereo- and regioselectivity in this biosynthesis, these structures further demonstrate that the ability of the two enzymes to distinguish between the A and B donors is largely determined by a single amino acid residue.
人类ABO(H)血型抗原由特定的糖基转移酶产生。N-乙酰半乳糖胺基转移酶（GTA）利用尿苷二磷酸-N-乙酰半乳糖胺（UDP-GalNAc）供体将H抗原受体转化为A抗原，而半乳糖基转移酶（GTB）则利用尿苷二磷酸半乳糖（UDP-半乳糖）供体将H抗原受体转化为B抗原。GTA和GTB仅在四个关键氨基酸残基的特性上有所不同。GTA和GTB酶在游离状态以及与二糖H抗原受体和UDP形成复合物时的分辨率为1.8 - 1.32埃的晶体结构揭示了供体和受体特异性的基础，并表明只有两个关键氨基酸残基能够与供体或受体底物接触。鉴于这种生物合成需要严格的立体和区域选择性，这些结构进一步证明，这两种酶区分A和B供体的能力在很大程度上由单个氨基酸残基决定。
