Phosphoglycerate Kinase
From Proteopedia
Mechanism of Phosphoglycerate Kinase(PGK) Catalysis
Phosphogylcerate kinase is a crucial enzyme of the glycolysis cycle. This cycle 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 GADPH reaction of the cycle.
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| 3cin, resolution 1.70Å () | |||||||||
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| Ligands: | , , | ||||||||
| Gene: | TM1419, TM_1419 (Thermotoga maritima MSB8) | ||||||||
| Activity: | Inositol-3-phosphate synthase, with EC number 5.5.1.4 | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum, TOPSAN | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
The SCOP classification of PGK is alpha and beta, indicating that is composed of roughly equal alpha and beta sheets. The tertiary stucture, or the overal structure, is that of a bilobed complex. The lobes/domains are clearly connected at only two locations: This enzyme has only one chain, thus its quaternary structure is that of a monomer.
The bilobed nature of the protein is very crucial in the its catlytic function. The active site is broken into two pieces, one on each interior lobe. On one site the ADP-Mg2+ substrate binds and on the other lobe the 1,3-Biphosphoglycerate substrate binds. Upon binding of both substrates at the active sites, the protein's conformation changes such that the two lobes of the protein swing together ([1] The hinge for this conformational change is beta sheet L and the new conformation is formed via a salt bridge between [2]== This swinging shut of the protein creates an interior hydrophobic chamber that is free of water for the reaction to take place in.
The mechanism of catalysis has not been established but must be similar to that of hexokinase. Hexokinase catalyzes the removal of a phosphate group from ATP to glucose and has a very similar structure and conformational change via a hinge. PGK has a similar function except it catalyzes the transfer of a phosphate to form ATP instead of using ATP. The reaction of PGK removes a phosphate group from the intermediate molecule, 1,3-biphosphoglycerate and transfers it to ADP to form ATP. Once the substrates bind to the active sites, the protein domains swing shut forcing the substrates into correct position for the reaction to proceed. [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.
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- ↑ Voet, Donald et al. 2008. Fundamentals of Biochemistry. 3rd ed. 499
- ↑ Blake and Rice. 1981. Phosphoglycerate kinase. Philosophical Transactions of the Royal Society of London. 293:93-104.
- ↑ Harnan, G. et al. 1992. Domain Motions in Phosphoglycerate Kinase: Determination of Interdomain Distance Distribution by Site Specific Labeling and Time Resolved Flourescense Energy Transfer. PNAS. 89:11764-11768.
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