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Revision as of 22:43, 27 February 2010

The Catalytic Ability of Phosphoglycerate Mutase

The Protein Data Bank Identification number for phosphoglyserate mutase (PGAM) is 1qhf^[1].

spinqualitylabelsall models PDB ID 1qhf Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
1qhf, resolution 1.70Å ()
Ligands:	,
Activity:	Phosphoglycerate mutase, with EC number 5.4.2.1
Structural annotation: Resources: CATH : 1Qhfa00, 1Qhfb00 InterPro : Ipr005952, Ipr001345, Ipr013078 Pfam : PF00300 SCOP : d1qhfa_, d1qhfb_ UniProt : P00950
Functional annotation: Cellular component: mitochondrion cytosol Biological process: gluconeogenesis glycolysis metabolic process Molecular function: catalytic activity intramolecular transferase activity, phosphotransferases protein binding bisphosphoglycerate mutase activity bisphosphoglycerate phosphatase activity phosphoglycerate mutase activity isomerase activity
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

In terms of the secondary structures, this protein is classified as an alpha/beta protein. Further, the fold is classified as “phosphoglycerate mutase-like”, having 3 main layers of alpha/beta/alpha. PGAM contains a mixed beta sheet of 6 strands, with strand 5 existing as an anti-parallel strand to the rest. The quaternary structure usually is comprised of two identical subunits, thus this enzyme can be classified as a homodimer. The dimers have a relative molecular mass of 56,000-60,000 kDa. ^[2] One exception includes the PGAM enzyme of yeast which is a homotetramer of mass 110,000 kDa. PGAM 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. Though the quaternary structure is the same in terms of the active site, several variations exist, called isozymes, which depend on the tissue in which the enzyme is active. Mm-type, mb-type, and bb-type are isozymes that catalyze glycolysis in smooth muscle, cardiac and skeletal muscle, and the remaining tissues, respectively.^[3] PGAM is an integral step in the process of glycolysis. Since this enzyme is a mutase, it will catalyze the transfer of a functional group from one position to another on a given substrate. It is responsible for the conversion of 3-phosphoglycerate (3PG) to 2-phosphoglycerate (2PG), having 2,3-bisphosphoglycerate as an intermediate. ^[4] With a Gibbs free energy of about 1.1 KJ/mol, this reaction is nearly energetically neutral. Despite this, it is absolutely necessary in order to generate the proper molecule needed to continue in the glycolytic pathway. The reaction that PGAM catalyzes is shown below.

          3PG + P-Enzyme → 2,3BPG + Enzyme → 2PG + P-Enzyme
  3-phosphoglycerate         intermediate          2-phosphoglycerate

It is important to note that the phosphate group that is placed on C2 is not the same phosphate group that was initially on C3. In order to understand how PGAM catalyzes this reaction, an explanation of its active site is imperative. The most important residues in this enzyme include two histidine residues with imidazole groups almost parallel to each other which are in close proximity to carbons 2 and 3 in the substrate. Based on crystallography experiments, the active site where these histidine residues reside lies at the bottom of a deep groove in each subunit. 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. ^[5] The phosphate group on C3 of the substrate is then transferred back onto His 8, thus regenerating the active from of the enzyme. In addition to the importance of the two histidine residues in the active site, the amino acids that line the active site are also functionally important. Several positively charged residues line the active site pocket, which are usually arginines. This structure is logical for its function because the enzyme binds a negatively charged substrate. The third and final important aspect of the active site is the presence of glutamate residues 15 and 86. 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.

1. ↑ Crowhurst GS, Dalby AR, Isupov MN, Campbell JW, Littlechild JA. Structure of a phosphoglycerate mutase:3-phosphoglyceric acid complex at 1.7 A. Acta Crystallogr D Biol Crystallogr. 1999 Nov;55(Pt 11):1822-6. PMID:10531478
2. ↑ S., Winn I., Fothergill A. L., Harkins N. R., and Watson C. H. "Structure and Activity of Phosphoglycerate Mutase." Sciences 293.1063 (1981): 121-30. Print.
3. ↑ "Phosphoglycerate mutase -." Wikipedia, the free encyclopedia. Web. 27 Feb. 2010. <http://en.wikipedia.org/wiki/Phosphoglycerate_mutase>.
4. ↑ Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry Life at the Molecular Level. New York: John Wiley & Sons, 2008. Print.
5. ↑ Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry Life at the Molecular Level. New York: John Wiley & Sons, 2008. Print.