Bisphosphoglycerate mutase

from Wikipedia, the free encyclopedia
Bisphosphoglycerate mutase
Bisphosphoglycerate mutase
Schematic representation of the Rapoport-Luebering cycle with the three enzyme activities of bisphosphoglycerate mutase

Existing structural data: s. UniProt

Properties of human protein
Mass / length primary structure 258 amino acids
Secondary to quaternary structure Homodimer
Identifier
Gene name BPGM
External IDs
Enzyme Classifications
EC, category 5.4.2.4 ,  phosphotransferase
Response type Rearrangement
Substrate 1,3-bisphosphoglycerate
Products 2,3-bisphosphoglycerate
EC, category 5.4.2.1 ,  phosphotransferase
Response type Rearrangement
Substrate 2-phosphoglycerate
Products 3-phosphoglycerate
EC, category 3.1.3.13 ,  phosphatase
Response type hydrolysis
Substrate 2,3-bisphosphoglycerate + H 2 O
Products 3-phosphoglycerate + phosphate

The bisphosphoglycerate mutase (BPGM), formerly referred to as 2,3-Diphosphoglyceratmutase referred to is an enzyme , which is primarily in the erythrocytes (red blood cells) and in erythropoetischem tissue of mammals occurs. It is in the red blood cells of the central enzyme Luebering-Rapoport pathway , a byway of glycolysis in which they as a trifunctional enzyme three different biochemical reactions for the formation and for the degradation of 2,3-bisphosphoglycerate (2,3-BPG) catalyzes . As a biochemical effector, 2,3-BPG is involved in the regulation of the binding capacity (affinity) of the blood pigment hemoglobin for the respiratory gas oxygen in the erythrocytes.

Features and function

On the one hand, bisphosphoglycerate mutase, as a synthase (2,3-DPG synthase, synonym bisphosphoglycerate mutase; EC  5.4.2.4 ), catalyzes the formation of 2,3-bisphosphoglycerate (2,3-BPG) from the 1,3-bisphosphoglycerate produced in glycolysis (1,3-BPG). In addition, it also functions as a phosphatase (2,3-bisphosphoglycerate phosphatase ; EC 3.1.3.13 ) for the conversion of 2,3-BPG to 3-phosphoglycerate (3-PG) and as a mutase (monophosphoglycerate mutase ; EC 5.4.2.1 ) for the the equilibrium reaction between the phosphoglyceric acid compounds 3-PG and 2-phosphoglycerate (2-PG).   

The BPGM has a common active center for the three different functions , which is equipped with two different binding sites for di- and monophosphoglycerates. The most important activity of the enzyme is the irreversible synthase reaction, which distinguishes it from phosphoglycerate mutase in the main route of glycolysis. This is similar to the BPGM in terms of molecular mass , subunit structure and amino acid sequence and also functions as a trifunctional enzyme, but with a different ratio of the three activities to each other.

The materially neutral rearrangement from 1,3-DPG to 2,3-DPG requires the presence of magnesium ions and has its pH optimum at around 7.2. The hydrolysis of 2,3-DPG to 3-PG takes place with the consumption of a water molecule and the release of an inorganic phosphate , and takes place more intensely at an acidic pH value. The amino acid sequence of human BPGM, which has a molar mass of 30,005 Daltons and a homodimeric structure , is 259 amino acids in length .

The 2,3-DPG formed in the Rapoport-Luebering cycle is an important biochemical effector for the regulation of the binding ability (affinity) of the blood pigment hemoglobin for the breathing gas oxygen . Accordingly, the bisphosphoglycerate mutase occurs mainly in the erythrocytes (red blood cells) and in the erythropoietic tissue of mammals . Other activities were also found in placental tissue and, to a much lesser extent, in the liver .

Discovery story

The reactions for the formation and cleavage of 2,3-bisphosphoglycerate were discovered by the Austro-American-German biochemist Samuel Mitja Rapoport and his technical assistant Janet Luebering in the United States in the 1940s and described in several publications in the early 1950s. In the 1960s and 1970s, the properties of the enzyme bisphosphoglycerate mutase and its trifunctional activity were characterized in more detail. The amino acid sequence of human BPGM was determined in 1983, the nucleotide sequence of the corresponding gene five years later. In 2004, the crystal structure of the enzyme molecule was published.

Individual evidence

  1. ↑ T. Fujita et al .: Human Erythrocyte Bisphosphoglycerate Mutase: Inactivation by Glycation In Vivo and In Vitro. In: Journal of Biochemistry . 124 (6 )/1998. Japanese Biochemical Society, pp. 1237-1244.
  2. ↑ a b Y. Wang et al .: Crystal Structure of Human Bisphosphoglycerate Mutase. In: Journal of Biological Chemistry . 279/2004. The American Society for Biochemistry and Molecular Biology, pp. 39132-39138.
  3. ↑ P. Ravel, CT Craescu, N. Arous, J. Rosa, MC Gare: Critical Role of Human Bisphosphoglycerate Mutase Cys 22 in the Phosphatase Activator-binding Site. In: Journal of Biological Chemistry . 272/1997. The American Society for Biochemistry and Molecular Biology, pp. 14045-14050.
  4. ↑ a b R. Sasaki, K. Ikura, E. Sugimoto, H. Chiba: Purification of bisphosphoglycerate mutase, bisphosphoglycerate phosphatase and phosphoglycerate mutase from human erythrocytes: three enzyme activities in one protein. In: European Journal of Biochemistry . 50 (3) / 1975. Federation of European Biochemical Societies, pp. 581-593.
  5. ↑ Gerhard Michal: Biochemical Pathways : Biochemistry Atlas. Spektrum Akademischer Verlag, Heidelberg 1999, ISBN 3-86025-239-9 , pp. 27/28.
  6. ↑ UniProt: Bisphosphoglycerate mutase - Homo sapiens (Human) (accessed November 26, 2008)
  7. ↑ DC Pritlove, M. Gu, CA Boyd, HS Randeva, M. Vatish: Novel placental expression of 2,3-bisphosphoglycerate mutase. In: Placenta. 27 (6) / 2006. WB Saunders, pp. 924-927.
  8. ↑ a b V. Joulin et al .: Isolation and characterization of the human 2,3-bisphosphoglycerate mutase gene. In: Journal of Biological Chemistry . 263/1988. The American Society for Biochemistry and Molecular Biology, pp. 15785-15790.
  9. ^ S. Rapoport, J. Luebering: The formation of 2,3-diphosphoglycerate in rabbit erythrocytes: The existence of a diphosphoglycerate mutase. In: Journal of Biological Chemistry . 183/1950. Pp. 507-516.
  10. ↑ S. Rapoport, J. Luebering: Glycerate-2,3-diphosphatase. In: Journal of Biological Chemistry . 189/1951. Pp. 683-694.
  11. ↑ ZB Rose: The Purification and Properties of Diphosphoglycerate Mutase from Human Erythrocytes. In: Journal of Biological Chemistry . 243 (18 )/1968. The American Society for Biochemistry and Molecular Biology, pp. 4810-4820.
  12. ^ NW Haggarty, B. Dunbar, LA Fothergill: The complete amino acid sequence of human erythrocyte diphosphoglycerate mutase. In: EMBO Journal . 2 (7) / 1983. Oxford University Press, pp. 1213-1220.

Web links