Correlation of Structure and Function in the Human Hotdog-fold Enzyme hTHEM4

详细信息    查看全文

• 作者：Hong Zhao ; Kap Lim ; Anthony Choudry ; John A. Latham ; Manish C. Pathak ; Dennis Dominguez ; Lusong Luo ; Osnat Herzberg ; Debra Dunaway-Mariano
• 刊名：Biochemistry
• 出版年：2012
• 出版时间：August 21, 2012
• 年：2012
• 卷：51
• 期：33
• 页码：6490-6492
• 全文大小：213K
• 年卷期：v.51,no.33(August 21, 2012)
• ISSN：1520-4995

文摘

Human THEM4 (hTHEM4) is comprised of a catalytically active hotdog-fold acyl-CoA thioesterase domain and an N-terminal domain of unknown fold and function. hTHEM4 has been linked to Akt1 regulation and cell apoptosis. Herein, we report the X-ray structure of hHTEM4 bound with undecan-2-one-CoA. Structure guided mutagenesis was carried out to confirm the catalytic residues. The N-terminal domain is shown to be partially comprised of irregular and flexible secondary structure, reminiscent of a protein-binding domain. We demonstrate direct hTHEM4-Akt1 binding by immunoprecipitation and by inhibition of Akt1 kinase activity, thus providing independent evidence that hTHEM4 is an Akt1 negative regulator.