title: Functional interaction of hexokinase with ATP requires participation by both small and large lobes of the enzyme: implications for other proteins using the actin fold as a nucleotide binding motif.
abstract: The actin fold is a structural motif involved in binding of ATP to an otherwise diverse family of proteins that includes hexokinase, actin, and the 70 kDa heat shock protein. Previous analyses have focused attention on a hydrophobic pocket within the large lobe of hexokinase (and analogous regions in other proteins possessing the actin fold motif) as the-site for binding of the adenine moiety. However, there is reason to believe that binding of the adenine moiety also involves a beta-sheet region located in the small lobe of hexokinase. It is postulated that functional interaction with ATP, required for catalysis, involves interactions with both regions. The expected structural consequences provide a basis for explaining the kinetic mechanism suggested for this enzyme, i.e., although both substrates can bind independently, the preferred kinetic pathway is not random but ordered, with glucose binding first. The structural features postulated to be involved in binding of ATP to hexokinase are also found in other proteins possessing the actin fold motif. Interaction of the nucleotide with the beta-sheet region, analogous to that found in the "small lobe" of hexokinase, may induce functionally important conformational changes in other proteins employing the actin fold as a nucleotide binding motif.
authors.affiliation: Department of Biochemistry, Michigan State University, East Lansing 48824-1319, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Wilson
authors.forename: D A
authors.initials: DA
authors.lastname: Schwab
mesh_terms: D000199:Actins / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D006593:Hexokinase / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000201:enzymology
chemical_list: D000199:Actins; D000255:Adenosine Triphosphate; D006593:Hexokinase