TY - JOUR
T1 - Identification and analysis of novel functional sites in human GD3-synthase
AU - Gu, Yihua
AU - Yu, Robert K.
N1 - Funding Information:
This work was supported by an NIH Grant (NS11853). We thank Dr. B.C. Wang, University of Georgia, Athens, for valuable suggestions during the course of this work. Acknowledgment is due to Dr. Rhea Markowitz for editorial assistance.
PY - 2008/5/23
Y1 - 2008/5/23
N2 - GD3-synthase is a sialyltransferase that catalyzes the synthesis of ganglioside GD3 leading to the b- and c-series gangliosides. It contains four common sequence regions of vertebrate sialyltransferases, referred to as the L, S, III, and VS sialylmotifs, which have been identified in all vertebrate sialyltransferases that play important roles in spatial structure maintenance and protein functions. No 3D structural information, however, is currently available for vertebrate sialyltransferases. Using primary sequence of human GD3-synthase, we identified the structure of a prokaryotic sialyltransferase (CstII, also known as an α2,3/α2,8-sialyltransferase) as the template for protein homology modeling. Secondary structural alignment between these two proteins identified several conserved amino-acid residues. The functions of four conserved residues (Asn188, Pro189, Ser190, and Arg272) between the L and S sialylmotifs in human GD3-synthase were investigated using mutational analysis and molecular modeling, and it was found that these sites are involved in determining the α2,8-linkage specificity of GD3-synthase.
AB - GD3-synthase is a sialyltransferase that catalyzes the synthesis of ganglioside GD3 leading to the b- and c-series gangliosides. It contains four common sequence regions of vertebrate sialyltransferases, referred to as the L, S, III, and VS sialylmotifs, which have been identified in all vertebrate sialyltransferases that play important roles in spatial structure maintenance and protein functions. No 3D structural information, however, is currently available for vertebrate sialyltransferases. Using primary sequence of human GD3-synthase, we identified the structure of a prokaryotic sialyltransferase (CstII, also known as an α2,3/α2,8-sialyltransferase) as the template for protein homology modeling. Secondary structural alignment between these two proteins identified several conserved amino-acid residues. The functions of four conserved residues (Asn188, Pro189, Ser190, and Arg272) between the L and S sialylmotifs in human GD3-synthase were investigated using mutational analysis and molecular modeling, and it was found that these sites are involved in determining the α2,8-linkage specificity of GD3-synthase.
KW - Functional site
KW - GD3-synthase
KW - Molecular modeling
KW - Sialyltransferase
KW - Site-directed mutagenesis
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U2 - 10.1016/j.bbrc.2008.03.029
DO - 10.1016/j.bbrc.2008.03.029
M3 - Article
C2 - 18348864
AN - SCOPUS:41849103006
SN - 0006-291X
VL - 370
SP - 67
EP - 71
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -