title: The crystal structure of human GDP-L-fucose synthase.
abstract: 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 reduction of the carbonyl at C-4. In this paper, the first crystal structure of human FX protein was determined at 2.37 Å 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 coli 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 α-helices 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.
authors.affiliation: Department of Biological Sciences, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhou
authors.forename: Lihua
authors.initials: L
authors.lastname: Sun
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Chunyan
authors.initials: C
authors.lastname: Xu
authors.forename: Feng
authors.initials: F
authors.lastname: Yu
authors.forename: Yahui
authors.initials: Y
authors.lastname: Liu
authors.forename: Chaoneng
authors.initials: C
authors.lastname: Ji
authors.forename: Jianhua
authors.initials: J
authors.lastname: He
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D055162:Biocatalysis; D002238:Carbohydrate Epimerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D006155:Guanosine Diphosphate Mannose / Q000031:analogs & derivatives / Q000378:metabolism; D006156:Guanosine Diphosphate Sugars / Q000378:metabolism; D006801:Humans; D007658:Ketone Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009249:NADP / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; C480160:GDP-gulose; D006156:Guanosine Diphosphate Sugars; D011994:Recombinant Proteins; C054686:GDP-4-keto-6-deoxymannose; D006155:Guanosine Diphosphate Mannose; D009249:NADP; C028277:TSTA3 protein, human; D007658:Ketone Oxidoreductases; D002238:Carbohydrate Epimerases
keywords: fx; gdp-l-fucose; gdp-l-fucose synthase