Structural highlightsFunctionODP2_CHATD The 10-megadalton pyruvate dehydrogenase complex contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3) and catalyzes the overall oxidative decarboxylation of pyruvate to form acetyl-CoA and CO(2) (PubMed:33567276, PubMed:34836937, PubMed:35093201). Within the complex, pyruvate and thiamine pyrophosphate (TPP or vitamin B1) are bound by pyruvate dehydrogenase E1 subunits alpha and beta and pyruvate is decarboxylated leading to the 2-carbon hydrohyethyl bound to TPP. The E2 component contains covalently-bound lipoyl cofactors and transfers the hydroxyethyl group from TPP to an oxidized form of covalently bound lipoamide, and the resulting acetyl group is then transferred to free coenzyme A to form acetyl-CoA and reduced dihydrolipoamide-E2. Finally, the flavoprotein dihydrolipoamide dehydrogenase (E3) re-oxidizes the lipoyl group of dihydrolipoamide-E2 to form lipoamide-E2 and NADH. A fourth subunit, E3BP, is responsible for tethering E3 in proximity to the core, forming the entire metabolon (Probable).[1] [2] [3] [4]
See AlsoReferences
- ↑ Kyrilis FL, Semchonok DA, Skalidis I, Tüting C, Hamdi F, O'Reilly FJ, Rappsilber J, Kastritis PL. Integrative structure of a 10-megadalton eukaryotic pyruvate dehydrogenase complex from native cell extracts. Cell Rep. 2021 Feb 9;34(6):108727. PMID:33567276 doi:10.1016/j.celrep.2021.108727
- ↑ Tuting C, Kyrilis FL, Muller J, Sorokina M, Skalidis I, Hamdi F, Sadian Y, Kastritis PL. Cryo-EM snapshots of a native lysate provide structural insights into a metabolon-embedded transacetylase reaction. Nat Commun. 2021 Nov 26;12(1):6933. doi: 10.1038/s41467-021-27287-4. PMID:34836937 doi:http://dx.doi.org/10.1038/s41467-021-27287-4
- ↑ Skalidis I, Kyrilis FL, Tuting C, Hamdi F, Chojnowski G, Kastritis PL. Cryo-EM and artificial intelligence visualize endogenous protein community members. Structure. 2022 Jan 19. pii: S0969-2126(22)00001-6. doi:, 10.1016/j.str.2022.01.001. PMID:35093201 doi:http://dx.doi.org/10.1016/j.str.2022.01.001
- ↑ Kyrilis FL, Semchonok DA, Skalidis I, Tüting C, Hamdi F, O'Reilly FJ, Rappsilber J, Kastritis PL. Integrative structure of a 10-megadalton eukaryotic pyruvate dehydrogenase complex from native cell extracts. Cell Rep. 2021 Feb 9;34(6):108727. PMID:33567276 doi:10.1016/j.celrep.2021.108727
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