title: Structural basis for the ADP-specificity of a novel glucokinase from a hyperthermophilic archaeon.
abstract: BACKGROUND
  ATP is the most common phosphoryl group donor for kinases. However, certain hyperthermophilic archaea such as Thermococcus litoralis and Pyrococcus furiosus utilize unusual ADP-dependent glucokinases and phosphofructokinases in their glycolytic pathways. These ADP-dependent kinases are homologous to each other but show no sequence similarity to any of the hitherto known ATP-dependent enzymes.
  
  
  RESULTS
  We solved the crystal structure at 2.3 A resolution of an ADP-dependent glucokinase from T. litoralis (tlGK) complexed with ADP. The overall structure can be divided into large and small alpha/beta domains, and the ADP molecule is buried in a shallow pocket in the large domain. Unexpectedly, the structure was similar to those of two ATP-dependent kinases, ribokinase and adenosine kinase. Comparison based on three-dimensional structure revealed that several motifs important both in structure and function are conserved, and the recognition of the alpha- and beta-phosphate of the ADP in the tlGK was almost identical with the recognition of the beta- and gamma-phosphate of ATP in these ATP-dependent kinases.
  
  
  CONCLUSIONS
  Noticeable points of our study are the first structure of ADP-dependent kinase, the structural similarity to members of the ATP-dependent ribokinase family, its rare nucleotide specificity caused by a shift in nucleotide binding position by one phosphate unit, and identification of the residues that discriminate ADP- and ATP-dependence. The strict conservation of the binding site for the terminal and adjacent phosphate moieties suggests a common ancestral origin of both the ATP- and ADP-dependent kinases.
authors: Department of Biotechnology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-Ku, Tokyo 113-8657, Japan.
authors: S
authors: S
authors: Ito
authors: S
authors: S
authors: Fushinobu
authors: I
authors: I
authors: Yoshioka
authors: S
authors: S
authors: Koga
authors: H
authors: H
authors: Matsuzawa
authors: T
authors: T
authors: Wakagi
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry*; D000248:Adenosine Kinase / Q000737:chemistry; D000595:Amino Acid Sequence; D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry; D018360:Crystallography, X-Ray; D005941:Glucokinase / Q000737:chemistry*; D008345:Manganese / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009711:Nucleotides / Q000737:chemistry; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013379:Substrate Specificity; D019712:Thermococcus / Q000737:chemistry*
chemical_list: D002241:Carbohydrates; D009711:Nucleotides; D008345:Manganese; D000244:Adenosine Diphosphate; C420842:ADP-dependent glucokinase; D017853:Phosphotransferases (Alcohol Group Acceptor); C022534:ribokinase; D005941:Glucokinase; D000248:Adenosine Kinase