Phosphoglycerate Kinase
From Proteopedia
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| + | 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:<scene name='Shane_Harmon_Sandbox/Domain_links/1'>Beta Sheet L, Residues 189-202 and between Alpha Helix 14 and 15, Residues 404-408</scene>. The SCOP clssification of PGK is alpha and beta, indicating that its secondary strucutre is composed of roughly equal numbers alpha and beta sheets. | ||
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| + | 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 teh 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 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:<scene name='Shane_Harmon_Sandbox/Domain_links/1'>Beta Sheet L, Residues 189-202 and between Alpha Helix 14 and 15, Residues 404-408</scene> This enzyme has only one chain, thus its quaternary structure is that of a monomer. | 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:<scene name='Shane_Harmon_Sandbox/Domain_links/1'>Beta Sheet L, Residues 189-202 and between Alpha Helix 14 and 15, Residues 404-408</scene> This enzyme has only one chain, thus its quaternary structure is that of a monomer. | ||
Revision as of 17:27, 22 March 2010
Mechanism of Phosphoglycerate Kinase(PGK) Catalysis
Phosphogylcerate kinase is a crucial enzyme of 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.
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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 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 teh 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]
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 [3] The hinge for this conformational change is beta sheet L and the new conformation is formed via a salt bridge between [4] 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. [5] 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.
- ↑ 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.
- ↑ 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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