4GAH

Human acyl-CoA thioesterases 4 in complex with undecan-2-one-CoA inhibitor

Summary for 4GAH

• Entry DOI: 10.2210/pdb4gah/pdb
• Descriptor: Thioesterase superfamily member 4, [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-oxidanyl-3-phosphonooxy-oxolan-2-yl]methoxy-oxidanyl-phosphoryl] [(3R)-2,2-dimethyl-3-oxidanyl-4-oxidanylidene-4-[[3-oxidanylidene-3-[2-[(2R)-2-oxidanylundecyl]sulfanylethylamino]propyl]amino]butyl] hydrogen phosphate (3 entities in total)
• Functional Keywords: hotdog fold, acyl coa hydrolase; akt c-terminal modulating protein, acyl-coa, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane: Q5T1C6
• Total number of polymer chains: 2
• Total formula weight: 50738.99

Authors

Lim, K.,Pathak, M.C.,Herzberg, O. (deposition date: 2012-07-25, release date: 2012-08-29, Last modification date: 2023-09-13)

Primary citation

Zhao, H.,Lim, K.,Choudry, A.,Latham, J.A.,Pathak, M.C.,Dominguez, D.,Luo, L.,Herzberg, O.,Dunaway-Mariano, D.
Correlation of structure and function in the human hotdog-fold enzyme hTHEM4.
Biochemistry, 51:6490-6492, 2012

PubMed 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.

PubMed: 22871024
DOI: 10.1021/bi300968n

Experimental method

X-RAY DIFFRACTION (2.3 Å)