Editing Pyruvate dehydrogenase complex (section)

==Structure==

=== Pyruvate dehydrogenase (E1) ===
[[File:E1 Subunit Ecoli.png|thumb|Pymol-generated image of E1 subunit of pyruvate dehydrogenase complex in E. Coli]]

The E1 subunit, called the [[pyruvate dehydrogenase]] subunit, is either a homodimer (comprising two “α” chains, e.g. in ''[[Escherichia coli]]'') or a heterotetramer of two different chains (two “α” and  two “β” chains). A magnesium ion forms a 4-coordinate complex with three, polar amino acid residues (Asp, Asn, and Tyr) located on the alpha chain, and the [[Thiamine pyrophosphate|thiamine diphosphate]] (TPP) cofactor directly involved in [[decarboxylation]] of the [[pyruvate]].<ref>{{cite journal |last1=Sgrignani |first1=J. |last2=Chen |first2=J. |last3=Alimonti |first3=A. |title=How phosphorylation influences E1 subunit pyruvate dehydrogenase: A computational study |journal=Scientific Reports |date=2018 |volume=8 |issue=14683 |page=14683 |doi=10.1038/s41598-018-33048-z |pmid=30279533 |pmc=6168537 |bibcode=2018NatSR...814683S |s2cid=52910721 |doi-access=free }}</ref><ref>[PBD ID: 2QTC] {{cite journal |last1=Kale |first1=S. |last2=Arjunan |first2=P. |last3=Furey |first3=W. |last4=Jordan |first4=F. |title=A dynamic loop at the active center of the Escherichia coli pyruvate dehydrogenase COMPLEX E1 component Modulates SUBSTRATE utilization and CHEMICAL communication with the E2 component |journal=Journal of Biological Chemistry |date=2007 |volume=282 |issue=38 |pages=28106–28116 |doi=10.1074/jbc.m704326200|pmid=17635929 |s2cid=25199383 |doi-access=free }}</ref>

=== Dihydrolipoyl transacetylase (E2) ===
The E2 subunit, or dihydrolipoyl acetyltransferase, for both prokaryotes and eukaryotes, is generally composed of three domains. The N-terminal domain (the lipoyl domain), consists of 1–3 lipoyl groups of approximately 80 amino acids each. The peripheral subunit binding domain (PSBD), serves as a selective binding site for other domains of the E1 and E3 subunits. Finally, the C-terminal (catalytic) domain catalyzes the transfer of acetyl groups and acetyl-CoA synthesis.<ref>{{cite journal |last1=Patel |first1=M. S. |last2=Nemeria |first2=N. S. |last3=Furey |first3=W. |last4=Jordan |first4=F. |title=The pyruvate dehydrogenase complexes: structure-based function and regulation |journal=The Journal of Biological Chemistry |date=2014 |volume=289 |issue=24 |pages=16615–16623 |doi=10.1074/jbc.R114.563148 |pmid=24798336 |pmc=4059105 |doi-access=free }}</ref> In Gammaproteobacteria, 24 copies of E2 form the cubic core of the pyruvate dehydrogenase complex, in which 8 E2 homotrimers are located at the vertices of the cubic core particle. 

=== Dihydrolipoyl dehydrogenase (E3) ===
[[File:E3 Subunit Putida.png|thumb|Pymol-generated E3 subunit of pyruvate dehydrogenase complex in Pseudomonas putida]]

The E3 subunit, called the [[Dihydrolipoyl dehydrogenase]] enzyme, is characterized as a [[homodimer]] protein wherein two [[cysteine]] residues, engaged in [[disulfide bonding]], and the FAD cofactor in the active site facilitate its main purpose as an oxidizing catalyst. One example of E3 structure, found in ''[[Pseudomonas putida]]'', is formed such that each individual homodimer subunit contains two binding domains responsible for FAD binding and NAD binding, as well as a central domain and an interface domain.<ref>{{cite journal |last1=Billgren |first1=E. S. |last2=Cicchillo |first2=R. M. |last3=Nesbitt |first3=N. M. |last4=Booker |first4=S. J. |title=Lipoic Acid Biosynthesis and Enzymology |journal=Comprehensive Natural Products |date=2010 |volume=2 |issue=7 |pages=181–212 |doi=10.1016/B978-008045382-8.00137-4 }}</ref><ref>[PDB ID: 1LVL] {{cite journal |last1=Mattevia |first1=A. |last2=Obmolova |first2=G. |last3=Sokatch |first3=J. R. |last4=Betzel |first4=C. |last5=Hol |first5=W. G. |title=The refined crystal STRUCTURE of pseudomonas Putida LIPOAMIDE DEHYDROGENASE complexed with NAD+ at 2.45 Å resolution |journal=Proteins: Structure, Function, and Genetics |date=1992 |volume=13 |issue=4 |pages=336–351 |doi=10.1002/prot.340130406|pmid=1325638 |s2cid=23288363 }}</ref>

=== Dihydrolipoyl dehydrogenase Binding protein (E3BP) ===
An auxiliary protein unique to most eukaryotes is the [[E3 binding protein]] (E3BP), which serves to bind the E3 subunit to the PDC complex. In the case of human E3BP, hydrophobic [[proline]] and [[leucine]] residues in the BP interact with the surface recognition site formed by the binding of two identical E3 monomers.<ref>{{cite journal |last1=Ciszak |first1=E. M. |last2=Makal |first2=A. |last3=Hong |first3=Y. S. |last4=Vettaikkorumakankauv |first4=A. K. |last5=Korotchkina |first5=L. G. |last6=Patel |first6=M. S. |title=How dihydrolipoamide dehydrogenase-binding protein binds dihydrolipoamide dehydrogenase in the human pyruvate dehydrogenase complex |journal=Journal of Biological Chemistry |date=2006 |volume=281 |issue=1 |pages=648–655 |doi=10.1074/jbc.m507850200|pmid=16263718 |s2cid=26797600 |doi-access=free }}</ref>