Ken Engle SANDBOX

From Proteopedia

Revision as of 19:26, 27 February 2010

Pyruvate, NADH, and ATP are the products of glycolysis. Under anaerobic conditions, pyruvate undergoes fermentation to oxidize NADH to NAD+, so glycolysis can continue. In alcoholic fermentation, which occurs in yeast, this is a two-step process. The first involves the Enzyme pyruvate decarboxylase (PDH). The pyruvate is decarboxylated to an acetaldehyde. This acetaldehyde then undergoes a reaction catalyzed by alcohol dehydrogenase to produce ethanol; this is the step in which the NAD+ is restored ^[1].

Pyruvate dehydrogenase is a homotetramer. One of the subunints is shown in Figure 1; this reveals that each identical subunit consists of approximately alternating α-helices and β-sheets, and 2 domains exist in each subunit ^[2]. The active site of PDH consists of Glu50, Glu 473, Asp27, and His114 according to Pei et al. (2010). Hydrogen bonding occurs between the substrate and Asp27, His114, and Thr72. In the catalytic step of the reaction mechanism, Glu473 donates a proton 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, the final step, 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^[3].

Thiamine diphosphate (ThDP) is an important cofactor in the pyruvate, acetaldehyde reaction. 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^[4].

spinqualitylabelsall models PDB ID 1zpd Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
1zpd, resolution 1.86Å ()
Ligands:	, ,
Activity:	Pyruvate decarboxylase, with EC number 4.1.1.1
Structural annotation: Resources: CATH : 1Zpda01, 1Zpda03, 1Zpda02, 1Zpdb01, 1Zpdb02, 1Zpdb03, 1Zpde02, 1Zpde03, 1Zpde01, 1Zpdf03, 1Zpdf01, 1Zpdf02 InterPro : Ipr012000, Ipr000399, Ipr012001, Ipr011766, Ipr012110 Pfam : PF02775, PF02776, PF00205 SCOP : d1zpda1, d1zpda3, d1zpda2, d1zpdb1, d1zpdb3, d1zpdb2, d1zpde3, d1zpde2, d1zpde1, d1zpdf1, d1zpdf2, d1zpdf3 UniProt : P06672
Functional annotation: Molecular function: magnesium ion binding carboxy-lyase activity thiamin pyrophosphate binding lyase activity pyruvate decarboxylase activity metal ion binding transferase activity catalytic activity
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

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. ↑ Pei XY, Erixon KM, Luisi BF, Leeper FJ. Structural Insights into the Prereaction State of Pyruvate Decarboxylase from Zymomonas mobilis . Biochemistry. 2010 Feb 5. PMID:20099870 doi:10.1021/bi901864j
4. ↑ Pei XY, Erixon KM, Luisi BF, Leeper FJ. Structural Insights into the Prereaction State of Pyruvate Decarboxylase from Zymomonas mobilis . Biochemistry. 2010 Feb 5. PMID:20099870 doi:10.1021/bi901864j