Bisphosphoglycerate mutase

Enzyme

Bisphosphoglycerate mutase (, BPGM) is an enzyme expressed in erythrocytes and placental cells. It is responsible for the catalytic synthesis of 2,3 Bisphosphoglycerate (2,3 BPG) from 1,3 bisphosphoglycerate. BPGM also has a mutase and a phosphatase function, but these are much less active, in contrast to its glycolytic cousin, phosphoglycerate mutase (PGM), which favors these two functions, but can also catalyze the synthesis of 2,3 BPG to a lesser extent.

Because the main function of bisphosphoglycerate mutase is the synthesis of 2,3 BPG, this enzyme is found only in erythrocytes and placental cells. as well as hydrogen bonding to substrate, as His 11, which it pulls into its catalytic position. Arg90: although not involved directly in binding, this positively charged residue is essential to overall stability of the protein. Can be substituted with Lysine with little effect on catalysis.

1,3 BPG binds to the active site, which causes a conformational change, in which the cleft around the active site closes in on the substrate, securely locking it in place. 1,3 BPG forms a large number of hydrogen bonds to the surrounding residues, many which are positively charged, severely restricting its mobility. Its rigidity suggests a very enthalpically driven association. Conformational changes cause His11 to rotate, partially aided by hydrogen bonding to His188. His11 is brought in–line with the phosphate group, and then goes through an SN2 mechanism in which His11 is the nucleophile that attacks the phosphate group. The 2’ hydroxy group then attacks the phosphate and removes it from His11, thereby creating 2,3 BPG.