Pyruvate decarboxylase: Difference between revisions

<StructureSection load='1qpb' size='450' side='right' scene='' caption='Pyruvate decarboxylate complex with pyruvamide (PDB code [[1qpb]])'>

The <scene name='40/401493/Active_site/1'>active site</scene> of PDC consists of Glu 477, Asp28,  His114, and His 115 as well as the thiamine diphosphate cofactor. Hydrogen bonding occurs between the substrate and Asp28, His114, and Thr73.  In the catalytic step of the reaction mechanism, <scene name='Ken_Engle_SANDBOX/Glu_473/2'>Glu 473</scene>, shown in red, donates a proton to the pyruvate. The scene shows the close proximity of this residue to the pyruvate. The negative charge of the Glu residue following the protonation of the substrate leads to the destabilization of the pyruvate carboxylate group. Next the carboxyl group leaves. Following decarboxylation in the final step of the mechanism, release of acetaldehyde, a proton is transferred to the Glu473 residue from a cofactor. After the protonation in a concerted step, a water molecule donates a proton to the substrate while receiving a proton from Glu473. As the proton is taken from the substrate, the electrons move to form a carbonyl, which leads to the release of the acetaldehyde<ref name="Pei" />.

Thiamine diphosphate (ThDP) is an important cofactor in alpha decarboxylation reactions.  The structure of ThDP is <scene name='40/401493/Bent_tpp/1'>bent</scene> when bound to the protein. This kink brings the 4'N of ThDP in close enough proximity to C2 to <scene name='40/401493/Deprotonation/2'>deprotonate</scene> it, forming a reactive ylid. Glutamic acid 51 on the other side of ThDP forms a <scene name='40/401493/Glu51_h_bond_to_thdp/1'>hydrogen bond</scene> with ThDP to increase the basicity of 4'N.  In the decarboxylation reaction, <scene name='40/401493/Tpp_c2/1'>C2</scene> of ThDP is deprotonated, and attacks C2 of the pyruvate (this structure has pyruvamide instead of pyruvate), resulting in a <scene name='40/401493/Tpp_c2_to_c2/1'>covalent bond</scene> between ThDP and the pyruvate.  This allows the ThDP to act as an electron sink for the decarboxylation reaction.