Phosphoglycerate Kinase
From Proteopedia
(→Mechanism of Phosphoglycerate Kinase(PGK) Catalysis) |
(→Mechanism of Phosphoglycerate Kinase(PGK) Catalysis) |
||
| Line 1: | Line 1: | ||
=Mechanism of Phosphoglycerate Kinase(PGK) Catalysis= | =Mechanism of Phosphoglycerate Kinase(PGK) Catalysis= | ||
| - | + | Phosphoglycerate kinase is a crucial enzyme in the glycolysis cycle. This cycle is a series of ten reactions which ultimately breaks down glucose into pyruvate while generating 2 NADH and 2 ATP molecules. Phosphogylcerate kinase is the seventh enzyme in the cycle which catalyzes the reaction of 1,3-Biphosphoglycerate and ADP to produce <scene name='Shane_Harmon_Sandbox/Product/1'>3-Phosphoglycerate</scene> and <scene name='Shane_Harmon_Sandbox/Atp/1'>ATP</scene>. This method for ATP production is known as substrate level phosphorylation because it produces energy storing ATP molecules with out the use of oxygen, NADH, or an ATPase. The reaction is highly exergonic allowing it to be coupled with the less thermodynamically favored GADPH reaction of the cycle so both reactions occur spontaneously.{{STRUCTURE_3cin | PDB=3PGK | SCENE= }} | |
| Line 6: | Line 6: | ||
| - | The bilobed structure of PGK is very crucial in its catalytic function. The active site is broken into two pieces, one on the interior of each lobe or domain. On one site the ADP-Mg2+ substrate binds and on the other lobe the 1,3-Biphosphoglycerate substrate binds. Upon binding of both substrate molecules at the active sites, the proteins conformation changes such that the two lobes of the protein swing together <ref>Voet, Donald et al. 2008. Fundamentals of Biochemistry. 3rd ed. 499 </ref> When the two domains swing shut, a hydrophobic chamber free from water is established where the reaction can take place. The hinge for this conformational change is beta sheet L and the new conformation is formed via a salt bridge between <scene name='Shane_Harmon_Sandbox/Salt_bridge/1'>ARG62 and ASP200.</scene> <ref>Blake and Rice. 1981. Phosphoglycerate kinase. Philosophical Transactions of the Royal Society of London. 293:93-104.</ref> | + | The bilobed structure of PGK is very crucial in its catalytic function. The active site is broken into two pieces, one on the interior of each lobe or domain. On one site the ADP-Mg2+ substrate binds and on the other lobe the 1,3-Biphosphoglycerate substrate binds. Upon binding of both substrate molecules at the active sites, the proteins conformation changes such that the two lobes of the protein swing together <ref>Voet, Donald et al. 2008. Fundamentals of Biochemistry. 3rd ed. 499 </ref> When the two domains swing shut, a hydrophobic chamber free from water is established where the reaction can take place. The hinge for this conformational change is beta sheet L and the new conformation is formed via a salt bridge between <scene name='Shane_Harmon_Sandbox/Salt_bridge/1'>ARG62 and ASP200.</scene> <ref>Blake and Rice. 1981. Phosphoglycerate kinase. Philosophical Transactions of the Royal Society of London. 293:93-104.</ref> Rescent research indicates that the mechanism for closure of the two domains is a series of hydrogen bond interactions that occur upon binding of the substrates on both domains <ref>Vas, M, Varga, A et al. 2010. Insight into the Mechanism of of Domain Movements and their Role in Enzyme Function: Example of 3-Phosphoglycerate kinase. Current Protein and Peptide Science. Jan 21, 2010. (Epub ahead of publication).<ref> |
| Line 15: | Line 15: | ||
The role of PGK in glycolysis is very important for the production of ATP through substrate level phosphorylation. Regulation of this protein is thus a result of its function. Recent research in frogs which can withstand freezing temperatures indicates that PGK is upregulated by the cold and more specifically by low levels of oxygen <ref> Shaobo, Wu et al. 2009. PGK1 expression responds to freezing, anoxia, and dehydration stresses in freeze tolerant wood frog, Rana sylvatica. Journal of Experimental Zoology. 311, 57-67 <ref> This makes logical sense as when oxygen is low, oxidative phosphorylation cannot occur. Thus without oxygen and oxidative phosphorylation, ATP levels begin to drop. In response to decreased ATP, PGK is upregulated to increase the amount of ATP produced by substrate level phosphorylation. It could therefore be expected that ADP might act to inhibit or downregulated PGK expression. | The role of PGK in glycolysis is very important for the production of ATP through substrate level phosphorylation. Regulation of this protein is thus a result of its function. Recent research in frogs which can withstand freezing temperatures indicates that PGK is upregulated by the cold and more specifically by low levels of oxygen <ref> Shaobo, Wu et al. 2009. PGK1 expression responds to freezing, anoxia, and dehydration stresses in freeze tolerant wood frog, Rana sylvatica. Journal of Experimental Zoology. 311, 57-67 <ref> This makes logical sense as when oxygen is low, oxidative phosphorylation cannot occur. Thus without oxygen and oxidative phosphorylation, ATP levels begin to drop. In response to decreased ATP, PGK is upregulated to increase the amount of ATP produced by substrate level phosphorylation. It could therefore be expected that ADP might act to inhibit or downregulated PGK expression. | ||
| - | |||
<references/> | <references/> | ||
<ref></ref> | <ref></ref> | ||
Revision as of 14:59, 23 March 2010
Mechanism of Phosphoglycerate Kinase(PGK) Catalysis
Phosphoglycerate kinase is a crucial enzyme in the glycolysis cycle. This cycle is a series of ten reactions which ultimately breaks down glucose into pyruvate while generating 2 NADH and 2 ATP molecules. Phosphogylcerate kinase is the seventh enzyme in the cycle which catalyzes the reaction of 1,3-Biphosphoglycerate and ADP to produce and . This method for ATP production is known as substrate level phosphorylation because it produces energy storing ATP molecules with out the use of oxygen, NADH, or an ATPase. The reaction is highly exergonic allowing it to be coupled with the less thermodynamically favored GADPH reaction of the cycle so both reactions occur spontaneously.
| |||||||||
| 3cin, resolution 1.70Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||||
| Gene: | TM1419, TM_1419 (Thermotoga maritima MSB8) | ||||||||
| Activity: | Inositol-3-phosphate synthase, with EC number 5.5.1.4 | ||||||||
| |||||||||
| |||||||||
| Resources: | FirstGlance, OCA, RCSB, PDBsum, TOPSAN | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
The overall structure of phosphoglycerate kinase is very distinctive. It is a monomeric protein consisting of XXXXX amino acids. The structure is distinctly bilobed with a depressed region between the two lobes or domains. The lobes/domains are clearly connected at only two locations:. The SCOP clssification of PGK is alpha and beta, indicating that its secondary strucutre is composed of roughly equal numbers alpha and beta sheets.
The bilobed structure of PGK is very crucial in its catalytic function. The active site is broken into two pieces, one on the interior of each lobe or domain. On one site the ADP-Mg2+ substrate binds and on the other lobe the 1,3-Biphosphoglycerate substrate binds. Upon binding of both substrate molecules at the active sites, the proteins conformation changes such that the two lobes of the protein swing together [1] When the two domains swing shut, a hydrophobic chamber free from water is established where the reaction can take place. The hinge for this conformational change is beta sheet L and the new conformation is formed via a salt bridge between [2] Rescent research indicates that the mechanism for closure of the two domains is a series of hydrogen bond interactions that occur upon binding of the substrates on both domains [3] The negatively charged oxygen of the last phosphate group on ADP nucelophillically attacks a phosphate of 1,3-phosphoglycerate. The product, ATP, is favored because it's negatively charged oxygens of the 3 phosphates form hydrogen bonds with the enzyme. The 3 hydrogen bonds of ATP is favored over the 2 hydrogen bonds of ADP.
The role of PGK in glycolysis is very important for the production of ATP through substrate level phosphorylation. Regulation of this protein is thus a result of its function. Recent research in frogs which can withstand freezing temperatures indicates that PGK is upregulated by the cold and more specifically by low levels of oxygen [4]
Proteopedia Page Contributors and Editors (what is this?)
Shane Harmon, Michal Harel, Joel L. Sussman, Brandon Tritle, David Canner, Alexander Berchansky
