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Bisphosphoglycerate mutase (, BPGM) is an enzyme unique to
erythrocytes Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
and
placental Placental mammals (infraclass Placentalia ) are one of the three extant subdivisions of the class Mammalia, the other two being Monotremata and Marsupialia. Placentalia contains the vast majority of extant mammals, which are partly distinguishe ...
cells. It is responsible for the catalytic synthesis of
2,3-Bisphosphoglycerate 2,3-Bisphosphoglyceric acid (conjugate base 2,3-bisphosphoglycerate) (2,3-BPG), also known as 2,3-diphosphoglyceric acid (conjugate base 2,3-diphosphoglycerate) (2,3-DPG), is a three-carbon isomer of the glycolytic intermediate 1,3-bisphosphoglyce ...
(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 :''This enzyme is not to be confused with Bisphosphoglycerate mutase which catalyzes the conversion of 1,3-bisphosphoglycerate to 2,3-bisphosphoglycerate.'' Phosphoglycerate mutase (PGM) is any enzyme that catalyzes step 8 of glycolysis - ...
(PGM), which favors these two functions, but can also catalyze the synthesis of 2,3-BPG to a lesser extent.


Tissue distribution

Because the main function of bisphosphoglycerate mutase is the synthesis of 2,3-BPG, this enzyme is found only in
erythrocytes Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
and
placental Placental mammals (infraclass Placentalia ) are one of the three extant subdivisions of the class Mammalia, the other two being Monotremata and Marsupialia. Placentalia contains the vast majority of extant mammals, which are partly distinguishe ...
cells. In glycolysis, converting 1,3-BPG to 2,3-BPG would be very inefficient, as it just adds another unnecessary step. Since the main role of 2,3-BPG is to shift the equilibrium of
hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...
toward the deoxy-state, its production is really only useful in the cells which contain hemoglobin- erythrocytes and placental cells.


Function

1,3-BPG is formed as an intermediate in glycolysis. BPGM then takes this and converts it to 2,3-BPG, which serves an important function in
oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...
transport. 2,3-BPG binds with high affinity to Hemoglobin, causing a conformational change that results in the release of oxygen. Local tissues can then pick up the free oxygen. This is also important in the placenta, where fetal and maternal blood come within such close proximity. With the placenta producing 2,3-BPG, a large amount of oxygen is released from nearby maternal hemoglobin, which can then dissociate and bind with fetal hemoglobin, which has a much lower affinity for 2,3-BPG.


Structure


Overall

BPGM is a dimer composed of two identical protein subunits, each with its own active site. Each subunit consists six β-strands, β A-F, and ten α-helices, α 1-10. Dimerization occurs along the faces of β C and α 3 of both monomers. BPGM is roughly 50% identical to its PGM counterpart, with the main active-site residues conserved in nearly all PGMs and BPGMs.


Important residues

*
His His or HIS may refer to: Computing * Hightech Information System, a Hong Kong graphics card company * Honeywell Information Systems * Hybrid intelligent system * Microsoft Host Integration Server Education * Hangzhou International School, in ...
11: the nucleophile of the 1,2-BPG to 1,3-BPG reaction. Rotates back and forth with the help of His-188 to get in an in-line position in order to attack the 1’ phosphate group. * His-188: involved in overall stability of protein, 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. * Cys23: has little effect on overall structure, but large effect on reactivity of the enzyme.


Mechanism of 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 In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a l ...
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.


References


Further reading

*


External links

* * {{DEFAULTSORT:Bisphosphoglycerate Mutase EC 5.4.2