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Biochemistry. 2012 Aug 21;51(33):6490-2. doi: 10.1021/bi300968n. Epub 2012 Aug 9.

Correlation of structure and function in the human hotdog-fold enzyme hTHEM4.

Author information

1
Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM 87131, USA.

Abstract

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.

PMID:
22871024
PMCID:
PMC4066673
DOI:
10.1021/bi300968n
[Indexed for MEDLINE]
Free PMC Article

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