Phosphoglycerate Mutase: Difference between revisions

{{STRUCTURE_1eqj| PDB=1eqj | SIZE=400| SCENE= |right|CAPTION=Yeast phosphoglycerate mutase complex with phosphoglyceric acid and sulfate, [[1eqj]] }}

[[Glycolysis]] is a 10-step process that invests energy in the initial stages only to recover greater amounts of energy in the final steps. Every step in this metabolic pathway is essential to the ultimate production of energy. Every step is catalyzed by one or more enzymes that enhance the rate of the given reaction. Phosphoglycerate mutase is the specific homotetramer enzyme that catalyzes step 8 of glycolysis transfering the phosphate from 3-phosphoglyceric acid to the second carbon to form 2-phosphoglyceric acid, having the Protein Data Bank ID [[1qhf]]<ref>PMID:10531478</ref>. '''Phosphoglycerate mutase''' (PGM) is found in organisms from yeast to humans because it plays a significant role in glycolysis, which is a highly conserved process across many taxa. A deficiency of this enzyme causes CNS symptoms, muscle weakness, cramps and fatigue with exercise.  '''2,3-bisphosphoglycerate-independent phosphoglycerate mutase''' (BIPGM) is found in archaea and eubacteria.  It catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglycerate.

 

<ref>http://disability.ucdavis.edu/disease_deatails.php?id=45</ref>

 

In order to understand how PGM catalyzes this reaction, an explanation of its active site is imperative.  The most important residues in this enzyme include <scene name='Christopher_Vachon_Sandbox/His_8_good/2'>His 8 and 179</scene> with imidazole groups which are in close proximity to carbons 2 and 3 in the substrate.  His-8 is phosphorylated during during catalysis, and it is likely that His-179 acts as the proton donor/acceptor <ref>Rose, Z.B. (1980) Adv. Enzymol. Relat. Areas Mol. Biol. 51, <scene name='Phosphoglycerate_Mutase/First_try/1'>TextToBeDisplayed</scene>211-253</ref>. Based on crystallography experiments, the active site where these histidine residues reside lies at the bottom of a deep groove in each subunit. <ref name="winn" />  The sites in each subunit, whether the enzyme is a homodimer or homotetramer, are well separated.  The active enzyme contains a phosphoryl group attached to His 8.  This phosphoryl group is what is transferred to C2 of the substrate, resulting in an intermediate 2,3-bisphosphoglycerate-enzyme complex.  Thus there is a <scene name='Christopher_Vachon_Sandbox/Good_active_site_scene/6'>covalently attached phosphate</scene> in the active monomer. <ref name="voet" /> The phosphate group on C3 of the substrate is then transferred back onto His 8, thus regenerating the active form of the enzyme.  

In addition to the importance of the two histidine residues in the active site, the amino acids that line the <scene name='Christopher_Vachon_Sandbox/Good_active_site_scene/5'>active site</scene> are also functionally important.  These residues include H179, H8, E15, S11, T20, R59, and E86.<ref name="voet" /> Several positively charged residues line the active site pocket. These residues usually tend to be <scene name='Christopher_Vachon_Sandbox/Arginine_residues/1'>arginine residues</scene>, which are important for the optimal activity of the enzyme. <ref name="winn" />  This structure is logical for its function because the enzyme binds a negatively charged substrate, thus a positively charged groove fosters tight binding with a negative substrate.  The third and final important aspect of the active site is the presence of <scene name='Christopher_Vachon_Sandbox/Glutamate_residues_2/1'>glutamate residues 15 and 86</scene>.<ref name="winn" />  It is suggested that the carboxyl groups of these amino acid residues act as proton-withdrawing groups as they flank both sides of the substrate.  

 

 

[[3o0t]], [[3mxo]] – hPGM5 residues 90-289 – human<br />

 

 

 

 

 

For additional information, see: [[Carbohydrate Metabolism]]