Editing Pyruvate dehydrogenase complex (section)

==Differences in structure and subunit composition between species==
In all organisms, PDC is a large complex composed of multiple copies of the three catalytic subunits E1, E2 and E3. Another common feature of all PDCs is the fact that the subunit E2 forms the core of the complex to which the peripheral subunits E1 and E3 bind. Eukaryotic PDCs contain an additional, non-catalytic subunit in the core termed E3 binding protein (E3BP) (sometimes also "protein X"). In PDCs with a hetero-oligomeric core with multiple copies of E2 and E3BP, E1 exclusively associates with E2, and E3 only binds to E3BP. In contrast, E1 and E3 compete for binding to E2 in bacterial PDCs with a homo-oligomeric E2 core. While the peripheral enzyme E3 is a homodimer in all organisms, the peripheral enzyme E1 is an alpha<sub>2</sub>beta<sub>2</sub> heterotetramerin eukaryotes.

===Gram-negative bacteria===
In [[Gram-negative]] bacteria, e.g. ''[[Escherichia coli]]'', PDC consists of a central cubic core made up from 24 molecules of [[dihydrolipoyl transacetylase]] (E2).
Up to 16 homodimers of [[pyruvate dehydrogenase]] (E1) and 8 homodimers  of [[dihydrolipoyl dehydrogenase]] (E3) bind to the 24 peripheral subunit binding domains (PSBDs) of the E2 24-mer.
In [[Gammaproteobacteria]], the specificity of PSBD for binding either E1 or E3 is determined by the oligomeric state of PSBD. In each E2 homotrimer, two of the three PSBDs dimerize. While two E1 homodimers cooperatively bind dimeric PSBD, the remaining, unpaired PSBD specifically interacts with one E3 homodimer. PSBD dimerization thus determines the subunit composition of the pyruvate dehydrogenase complex when fully saturated with the peripheral subunits E1 and E3, which has a stoichiometry of E1:E2:E3 (monomers) = 32:24:16 
<ref>{{cite journal |vauthors=Meinhold S, Zdanowicz R, Giese C, Glockshuber R |year=2024 |title=Dimerization of a 5-kDa domain defines the architecture of the 5-MDa gammaproteobacterial pyruvate dehydrogenase complex |journal=Sci. Adv. |volume=10 |issue=6 |pages=eadj6358 |bibcode=2024SciA...10J6358M |doi=10.1126/sciadv.adj6358 |pmc=10849603 |pmid=38324697 |doi-access=free}} [http://www.pnas.org/cgi/content/abstract/96/4/1240]</ref> 

===Gram-positive bacteria and eukaryotes===
In contrast, in [[Gram-positive]] bacteria (e.g. ''[[Bacillus stearothermophilus]]'') and eukaryotes the central PDC core contains 60 E2 molecules arranged into an icosahedron. This E2 subunit “core” coordinates to 30 subunits of E1 and 12 copies of E3.

Eukaryotes also contain 12 copies of an additional core protein, [[E3 binding protein]] (E3BP) which bind the E3 subunits to the E2 core.<ref>{{cite journal |last1=Brautigam |first1=C. A. |last2=Wynn |first2=R. M. |last3=Chuang |first3=J. L. |last4=Machius |first4=M. |last5=Tomchick |first5=D. R. |last6=Chuang |first6=D. T. |title=Structural insight into interactions between Dihydrolipoamide Dehydrogenase (E3) and E3 binding protein of Human pyruvate dehydrogenase complex |journal=Structure |date=2006 |volume=14 |issue=3 |pages=611–621 |doi=10.1016/j.str.2006.01.001|pmid=16442803 |pmc=2879633 }}</ref>  The exact location of E3BP is not completely clear. Cryo-electron microscopy has established that E3BP binds to each of the icosahedral faces in yeast.<ref>Stoops, J.K., Cheng, R.H., Yazdi, M.A., Maeng, C.Y., Schroeter, J.P., Klueppelberg, U., Kolodziej, S.J., Baker, T.S., Reed, L.J. (1997) On the unique structural organization of the Saccharomyces cerevisiae pyruvate dehydrogenase complex. J. Biol. Chem. 272, 5757-5764.</ref> However, it has been suggested that it replaces an equivalent number of E2 molecules in the bovine PDC core.

Up to 60 E1 or E3 molecules can associate with the E2 core from Gram-positive bacteria - binding is mutually exclusive. In eukaryotes E1 is specifically bound by E2, while E3 associates with E3BP. It is thought that up to 30 E1 and 6 E3 enzymes are present, although the exact number of molecules can vary ''in vivo'' and often reflects the metabolic requirements of the tissue in question.