6TNM

E. coli aerobic trifunctional enzyme subunit-alpha

Summary for 6TNM

• Entry DOI: 10.2210/pdb6tnm/pdb
• Descriptor: Fatty acid oxidation complex subunit alpha, GLYCEROL, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: fatty acid oxidation, lipid metabolism, hydratase, dehydrogenase, trifunctional enzyme, beta oxidation, oxidoreductase
• Biological source: Escherichia coli (strain K12)
• Total number of polymer chains: 1
• Total formula weight: 82341.78

Authors

Sah-Teli, S.K.,Hynonen, M.J.,Wierenga, R.K.,Venkatesan, R. (deposition date: 2019-12-09, release date: 2020-03-25, Last modification date: 2024-01-24)

Primary citation

Sah-Teli, S.K.,Hynonen, M.J.,Sulu, R.,Dalwani, S.,Schmitz, W.,Wierenga, R.K.,Venkatesan, R.
Insights into the stability and substrate specificity of the E. coli aerobic beta-oxidation trifunctional enzyme complex.
J.Struct.Biol., 210:107494-107494, 2020

PubMed Abstract: Degradation of fatty acids by the β-oxidation pathway results in the formation of acetyl-CoA which enters the TCA cycle for the production of ATP. In E. coli, the last three steps of the β-oxidation are catalyzed by two heterotetrameric αβ enzymes namely the aerobic trifunctional enzyme (EcTFE) and the anaerobic TFE (anEcTFE). The α-subunit of TFE has 2E-enoyl-CoA hydratase (ECH) and 3S-hydroxyacyl-CoA dehydrogenase (HAD) activities whereas the β-subunit is a thiolase with 3-ketoacyl-CoA thiolase (KAT) activity. Recently, it has been shown that the two TFEs have complementary substrate specificities allowing for the complete degradation of long chain fatty acyl-CoAs into acetyl-CoA under aerobic conditions. Also, it has been shown that the tetrameric EcTFE and anEcTFE assemblies are similar to the TFEs of Pseudomans fragi and human, respectively. Here the properties of the EcTFE subunits are further characterized. Strikingly, it is observed that when expressed separately, EcTFE-α is a catalytically active monomer whereas EcTFE-β is inactive. However, when mixed together active EcTFE tetramer is reconstituted. The crystal structure of the EcTFE-α chain is also reported, complexed with ATP, bound in its HAD active site. Structural comparisons show that the EcTFE hydratase active site has a relatively small fatty acyl tail binding pocket when compared to other TFEs in good agreement with its preferred specificity for short chain 2E-enoyl-CoA substrates. Furthermore, it is observed that millimolar concentrations of ATP destabilize the EcTFE complex, and this may have implications for the ATP-mediated regulation of β-oxidation in E. coli.

PubMed: 32171906
DOI: 10.1016/j.jsb.2020.107494

Experimental method

X-RAY DIFFRACTION (2.95 Å)