Sandbox 160
From Proteopedia
Introduction
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| 1vc2, resolution 2.60Å () | |||||||||
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| Activity: | Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating), with EC number 1.2.1.12 | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum, TOPSAN | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Glyceraldehyde 3-Phosphate dehydrogenase (GAPDH) is an Oxidoreductase enzyme and is involved in many important biochemical reactions. This protein is responsible for catalyzing the conversion of glyceraldeyde 3-Phosphate into 1,3-Biphosphoglycerate in a two step coupled mechanism. This conversion occurs during step 6 or the beginning of the "payoff phase" of glycolysis (the second half of the entire process) in which ATP and NADH is produced. A total of 2 NADH and 4 ATP are produced during this phase for a net gain of 2 NADH and 2 ATP for the entire glycolysis pathway per glucose.
Structure & Function
The enzyme contains a NAD+ group which functions as a hydrogen acceptor during the course of the reaction which is bound to a Rossman fold. During the catalysis of glyceraldehyde 3-phosphate to 1,3-biphosphoglycerate a hydride ion is enzymatically transferred from the aldehyde group of glyceraldehyde 3-phosphate to the nicotinamide ring of NAD+ reducing it to NADH (pink). The active site of GAPDH contains a cysteine (Cys149 colored green) residue which reacts with the glyceraldehyde 3-phosphate molecule through its -SH group. The substrate is covalently bound during the reaction through its aldehyde group to the -SH group and the reaction produces a thiohemiacetal. The of the molecule is illustrated below.
Active Site in Detail
Once Glyceraldehyde 3-phophate comes into contact with the active site it forms a hydrogen bond through its C2 hydroxyl group to Cys149N. The C1 hydroxyl group of the substrate binds to His176NE2. Additional hydrogen bonds to the phosphate group of the substrate from additional residues such as Thr1790G1,Arg231NH1 along with N7N and 02'N if the NAD+ moeity help stabilize the molecule during the course of the reaction in the active site. The nicotinamide ring of the NAD+ ligand is responsible for orienting the hydrogen atom at C1 towards itself which allows for easier transfer in producing in reducing NAD+ to NADH.
