The crystal structure of human GDP-L-fucose synthase  

作　　者：Huan Zhou Lihua Sun Jian Li Chunyan Xu Feng yu Yahui Liu Chaoneng Ji Jianhua He 

机构地区：[1]Department of Biological Sciences, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201204, China [2]State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China

出　　处：《Acta Biochimica et Biophysica Sinica》2013年第9期720-725,共6页生物化学与生物物理学报（英文版）

基　　金：This work was supported by grants from the Ministry of Science and Technology of China （No. 2011CB911102） and the National Natural Science Foundation of China （No. 31100528）.

摘　　要：Human GDP-L-fucose synthase, also known as FX protein, synthesizes GDP-L-fucose from its substrate GDP-4-keto-6- deoxy-D-mannose. The reaction involves epimerization at both C-3 and C-5 followed by an NADPH-dependent re- duction of the carbonyl at C-4. In this paper, the first crystal structure of human FX protein was determined at 2.37 resolution. The asymmetric unit of the crystal structure contains four molecules which form two homodimers. Each molecule consists of two domains, a Rossmann-fold NADPH- binding motif and a carboxyl terminal domain. Compared with the Escherichia coil GDP-L-fucose synthase, the overall structures of these two enzymes have four major differences. There are four loops in the structure of human FX protein corresponding to two oL-hehces and two β-sheets in that of the E. coli enzyme. Besides, there are seven different amino acid residues binding with NAPDH comparing human FX protein with that from E. coli. The structure of human FX reveals the key catalytic residues and could be useful for the design of drugs for the treatment of inflammation, auto- immune diseases, and possibly certain types of cancer.Human GDP-L-fucose synthase, also known as FX protein, synthesizes GDP-L-fucose from its substrate GDP-4-keto-6- deoxy-D-mannose. The reaction involves epimerization at both C-3 and C-5 followed by an NADPH-dependent re- duction of the carbonyl at C-4. In this paper, the first crystal structure of human FX protein was determined at 2.37 resolution. The asymmetric unit of the crystal structure contains four molecules which form two homodimers. Each molecule consists of two domains, a Rossmann-fold NADPH- binding motif and a carboxyl terminal domain. Compared with the Escherichia coil GDP-L-fucose synthase, the overall structures of these two enzymes have four major differences. There are four loops in the structure of human FX protein corresponding to two oL-hehces and two β-sheets in that of the E. coli enzyme. Besides, there are seven different amino acid residues binding with NAPDH comparing human FX protein with that from E. coli. The structure of human FX reveals the key catalytic residues and could be useful for the design of drugs for the treatment of inflammation, auto- immune diseases, and possibly certain types of cancer.

关 键 词：gdp-e-fucose synthase gdp-L-fucose fx 

分 类 号：Q55[生物学—生物化学] O614.121[理学—无机化学]