Pyruvate decarboxylase

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==Active Site==
==Active Site==
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The active site of PDC in ''Zymomonas mobilis'' consists of Glu50, Glu 473, Asp27, and His114<ref name="Pei" />. Hydrogen bonding occurs between the substrate and Asp27, His114, and Thr72. Yeast active site residues are similar. 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" />.
The active site of PDC in ''Zymomonas mobilis'' consists of Glu50, Glu 473, Asp27, and His114<ref name="Pei" />. Hydrogen bonding occurs between the substrate and Asp27, His114, and Thr72. Yeast active site residues are similar. 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" />.
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==ThDP an Important Cofactor==
==ThDP an Important Cofactor==
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Thiamine diphosphate (ThDP) is an important cofactor in the pyruvate, acetaldehyde reaction. The <scene name='Ken_Engle_SANDBOX/Diphosphate_groups/2'>orange diphosphate group</scene> of this cofactor can be seen in this scene near the four active sites though they are hidden in other scenes by the ligand, pyruvate. ThDP actually binds the substrate during the first step of the reaction at C2 of the pyruvate. It is this ThDP that changes the environment of the active site which leads to the protonation or deprotonation of Glu473. When ThDP is not bound, the active site is not even open to bind pyruvate. When it binds, it causes a conformational change, moving Glu473 in such a way that forms a pocket for pyruvate’s methyl group<ref name="Pei">PMID: 20099870 </ref>.
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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.
</StructureSection>
</StructureSection>
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Revision as of 20:51, 6 April 2022

Pyruvate decarboxylate complex with phosphono ester, citrate and Mg+2 ion (green) (PDB code 1zpd)

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3D structures of pyruvate decarboxylase

Updated on 06-April-2022

Additional Resources

For additional information, see: Carbohydrate Metabolism

References

  1. ↑ Garrett, R.H., & Grisham, C.M. (2007). Biochemistry. Belmont, CA: Thompson.
  2. ↑ Dobritzsch D, Konig S, Schneider G, Lu G. High resolution crystal structure of pyruvate decarboxylase from Zymomonas mobilis. Implications for substrate activation in pyruvate decarboxylases. J Biol Chem. 1998 Aug 7;273(32):20196-204. PMID:9685367
  3. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Pei
  4. ↑ Sergienko EA, Jordan F. Catalytic acid-base groups in yeast pyruvate decarboxylase. 3. A steady-state kinetic model consistent with the behavior of both wild-type and variant enzymes at all relevant pH values. Biochemistry. 2001 Jun 26;40(25):7382-403. PMID:11412092
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