The structure of mammalian hexokinase-1.
We have determined the structures of the glucose-6-phosphate (G6P)-inhibitable 100,000 Mr Type I hexokinase from rat and the G6P-sensitive 50,000 Mr hexokinase from Schistosoma mansoni at a resolution of 2.8 and 2.6 A respectively. The structures define the glucose and G6P binding sites in these enzymes, suggest the mechanisms of intradomain G6P inhibition and activity loss in the Type I hexokinase N-terminal half, and reveal the structure of the membrane targeting motif that integrates the Type I hexokinase into the outer mitochondrial membrane.
Mulichak
A M
AM
Department of Biochemistry, Michigan State University, East Lansing, USA. mulichak@alecto.bch.msu.edu
Wilson
J E
JE
Padmanabhan
K
K
Garavito
R M
RM
D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D019298:Glucose-6-Phosphate / Q000737:chemistry / Q000378:metabolism; D006593:Hexokinase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats; D012550:Schistosoma mansoni / Q000201:enzymology
D004791:Enzyme Inhibitors; D019298:Glucose-6-Phosphate; D006593:Hexokinase; D005947:Glucose