Structural and mechanistic insights into the bifunctional enzyme isocitrate dehydrogenase kinase/phosphatase AceK.
The switch between the Krebs cycle and the glyoxylate bypass is controlled by isocitrate dehydrogenase kinase/phosphatase (AceK). AceK, a bifunctional enzyme, phosphorylates and dephosphorylates isocitrate dehydrogenase (IDH) with its unique active site that harbours both the kinase and ATP/ADP-dependent phosphatase activities. AceK was the first example of prokaryotic phosphorylation identified, and the recent characterization of the structures of AceK and its complex with its protein substrate, IDH, now offers a new understanding of both previous and future endeavours. AceK is structurally similar to the eukaryotic protein kinase superfamily, sharing many of the familiar catalytic and regulatory motifs, demonstrating a close evolutionary relationship. Although the active site is shared by both the kinase and phosphatase functions, the catalytic residues needed for phosphatase function are readily seen when compared with the DXDX(T/V) family of phosphatases, despite the fact that the phosphatase function of AceK is strictly ATP/ADP-dependent. Structural analysis has also allowed a detailed look at regulation and its stringent requirements for interacting with IDH.
College of Chemistry, Beijing Normal University, Beijing 100875, People's Republic of China.
Jimin
J
Zheng
Susan P
SP
Yates
Zongchao
Z
Jia
D000249:Adenosine Monophosphate / Q000737:chemistry; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D004789:Enzyme Activation; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D057927:Hydrophobic and Hydrophilic Interactions; D007521:Isocitrate Dehydrogenase; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000737:chemistry* / Q000235:genetics; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D029968:Escherichia coli Proteins; D009097:Multienzyme Complexes; D000249:Adenosine Monophosphate; C548023:AceK protein, E coli; D007521:Isocitrate Dehydrogenase; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases