The sugar kinase/heat shock protein 70/actin superfamily: implications of conserved structure for mechanism.
Sugar kinases, stress-70 proteins, and actin belong to a superfamily defined by a fold consisting of two domains with the topology beta beta beta alpha beta alpha beta alpha. These enzymes catalyze ATP phosphoryl transfer or hydrolysis coupled to a large conformational change in which the two domains close around the nucleotide. The beta 1-beta 2 turns of each domain form hydrogen bonds with ATP phosphates, and conserved Asp, Glu or Gln residues coordinate Mg2+ or Ca2+ through bound waters. The activity of superfamily members is regulated by various effectors, some of which act by promoting or inhibiting the conformational change. Nucleotide hydrolysis eliminates interdomain bridging interactions between the second beta 1-beta 2 turn and the ATP gamma-phosphate. This is proposed to destabilize the closed conformation and affect the orientation of the two domains, which might in turn regulate the activity of kinase oligomers, stress-70 protein-protein complexes, and actin filaments.
Hurley
J H
JH
Laboratory of Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0580, USA.
D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000495:Allosteric Site; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000502:physiology; D008969:Molecular Sequence Data; D005810:Multigene Family; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
D000199:Actins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D000255:Adenosine Triphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor)