Functional interactions between the noncovalently associated N- and C-terminal halves of mammalian Type I hexokinase.
The 100 kDa Type I isozyme of mammalian hexokinase has evolved by duplication and fusion of a gene encoding an ancestral 50 kDa hexokinase. Although the N- and C-terminal halves are similar in sequence, they differ in function, catalytic activity being associated only with the C-terminal half while the N-terminal half serves a regulatory role. The N- and C-terminal halves of rat Type I hexokinase have been coexpressed in M + R 42 cells. The halves associate noncovalently to produce a 100 kDa form that exhibits characteristics seen with the intact Type I isozyme but not with the isolated catalytic C-terminal half, i.e., characteristics that are influenced by interactions between the halves. These include a decreased K(m) for the substrate ATP and the ability of P(i) to antagonize inhibition by Glc-6-P or its analog, 1-5-anhydroglucitol-6-P. Thus, functional interactions between the N- and C-terminal halves do not require their covalent linkage.
Sui
Dexin
D
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing 48824, USA.
Wilson
John E
JE
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D019143:Evolution, Molecular; D006593:Hexokinase / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D015394:Molecular Structure; D008970:Molecular Weight; D020836:Protein Structure, Quaternary; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D011994:Recombinant Proteins; D006593:Hexokinase