Phosphoglycerate Kinase: Difference between revisions

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== PGK in the Glycolysis Cycle ==
== PGK in the Glycolysis Cycle ==


'''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. Phosphoglycerate 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/2'>3-Phosphoglycerate</scene> and <scene name='Shane_Harmon_Sandbox/Atp/4'>ATP</scene>. This method for ATP production is known as substrate-level phosphorylation because it produces energy storing ATP molecules without 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. See [[Glycolysis Enzymes]].
'''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. Phosphoglycerate 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/2'>3-Phosphoglycerate</scene> and <scene name='Shane_Harmon_Sandbox/Atp/4'>ATP</scene>. This method for ATP production is known as substrate-level phosphorylation because it produces energy storing ATP molecules without 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. See [[Glycolysis Enzymes]], [[Gluconeogenesis]].


== Structure ==
== Structure ==
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Recent study of PGK has revolved around its function in tumor formation and growth. It has been shown that in addition to catalyzing its normal reaction of 1,3-Biphosphoglycerate and ADP to ATP and 3-Phosphoglycerate, PGK can also function to cleave disulfide bonds. Specifically, the review of sulfide bond cleavage indicates PGK has been shown to cleave disulfide bonds in the protein zymogen plasmin to produce the active form of the protein. The active form of plasmin is responsible for angiogenesis or blood vessel formation in tumors<ref>PMID:12189052</ref>  Without the formation of blood vessels in tumors, nutrients are limited and tumor growth is therfore limited. Once blood vessels are established growth can rapidly increase. The fact that tumor cells secrete PGK to allow blood vessel formation through the activation of the zymogen plasmin has important implications for understanding its regulation. If the regulation of PGK in tumor cells can be understood, it might be possible to inhibit the overproduction and secretion of PGK to limit angiogenesis in tumors.  
Recent study of PGK has revolved around its function in tumor formation and growth. It has been shown that in addition to catalyzing its normal reaction of 1,3-Biphosphoglycerate and ADP to ATP and 3-Phosphoglycerate, PGK can also function to cleave disulfide bonds. Specifically, the review of sulfide bond cleavage indicates PGK has been shown to cleave disulfide bonds in the protein zymogen plasmin to produce the active form of the protein. The active form of plasmin is responsible for angiogenesis or blood vessel formation in tumors<ref>PMID:12189052</ref>  Without the formation of blood vessels in tumors, nutrients are limited and tumor growth is therfore limited. Once blood vessels are established growth can rapidly increase. The fact that tumor cells secrete PGK to allow blood vessel formation through the activation of the zymogen plasmin has important implications for understanding its regulation. If the regulation of PGK in tumor cells can be understood, it might be possible to inhibit the overproduction and secretion of PGK to limit angiogenesis in tumors.  
</StructureSection>


==3D structures of phosphoglycerate kinase ==
==3D structures of phosphoglycerate kinase ==
[[Phosphoglycerate kinase 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*'''Phosphoglycerate kinase'''
 
**[[3oz7]], [[3oza]] – PfPGK – ''Plasmodium falciparum''<BR />
**[[3q3v]] – PGK – ''Campylobacter jejuni''<BR />
**[[2p9q]] – mPGK2 – mouse<BR />
**[[2ie8]] – PGK – ''Thermus caldophilus''<BR />
**[[1zmr]] – PGK – ''Escherichia coli''<BR />
**[[1v6s]] – PGK – ''Thermos thermophilus''<BR />
**[[1fw8]] – yPGK – yeast<BR />
**[[2pgk]] – PGK – horse<br />
**[[3uwd]] - PGK – ''Bacillus anthracis''<br />
**[[4dg5]] – PGK – ''Staphylococcus aureus''<br />
**[[4ehj]] – FtPGK – ''Francisella tularensis''<br />
**[[5bt8]] – PGK – ''Acinetobacter baumannii''<br />
 
*Phosphoglycerate kinase binary complex
 
**[[1vjc]] – pPGK + MgATP – pig<BR />
**[[1vjd]] - pPGK + ATP<BR />
**[[1ltk]] – PfPGK + AMP<BR />
**[[16pk]]– TbPGK (mutant) + bisubstrate analog – ''Trypanosoma brucei''<BR />
**[[1php]] – PGK + ADP – ''Geobacillus stearothermophilus''<BR />
**[[4fey]] – FtPGK + ADP<br />
**[[1vpe]] – PGK + ANP – ''Thermotoga maritima''<BR />
**[[2cun]] – PGK + PGA – ''Pyrococcus horikoshii''<BR />
**[[2p9t]] – mPGK2 + PGA<BR />
**[[2xe6]], [[3c39]] – hPGK1 + PGA - human<BR />
**[[2zgv]] - hPGK1 + ADP<BR />
**[[5o7d]], [[5mxm]], [[5m6z]], [[5m3u]], [[5m1r]] – hPGK1 (mutant) + ADP <br />
**[[5np8]] – hPGK1 + inhibitor <br />
**[[3c3b]], [[3c3c]] - hPGK1 + CDP <br />
**[[3zoz]] – hPGK1 + Br<br />
**[[3zlb]] - PGK + ANP – ''Streptococcus pneumoniae''<br />
**[[4ng4]] – PGK + ADP – ''Coxiella burnetii''<br />
 
*Phosphoglycerate kinase ternary complex
 
**[[2paa]] - mPGK2 + ATP + PGA<BR />
**[[1hdi]] - mPGK + MgATP + PGA<BR />
**[[1kf0]] - mPGK + AMPPCP + PGA<BR />
**[[1qpg]] - yPGK + MgATP + PGA<BR />
**[[3pgk]] - yPGK + ATP + PGA<BR />
**[[13pk]] - TbPGK + ADP + PGA<BR />
**[[2y3i]], [[2ybe]], [[2xe7]], [[2x13]], [[3c3a]] – hPGK1 + ADP + PGA <BR />
**[[2x15]] - hPGK1 + bisphosphoglycerate + ADP<br />
**[[2xe8]] - hPGK1 + AMPPNP + PGA<BR />
**[[2x14]] - hPGK1 (mutant) + AMPPCP + PGA<BR />
**[[2wzb]] - hPGK1 + ADP + MgF3 + PGA<BR />
**[[4axx]] - hPGK1 + ADP + BeF3 + 3PG<br />
**[[4o33]] - hPGK1 + terazosin + 3PG<br />
**[[4o3f]] - mPGK1 + terazosin + 3PG<br />
**[[2wzc]] - hPGK1 + ADP + AlF4 + PGA<BR />
**[[2wzd]] - hPGK1 (mutant) + ADP + AlF3 + PGA<BR />
}}
 
 
 
 
 


==Additional Resources==
==Additional Resources==

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Shane Harmon, David Canner, Brandon Tritle, Michal Harel, Alexander Berchansky, Joel L. Sussman