Transcript Enzyme review

Enzyme review
Made by Pisarev Vladimir
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Name: Human Phosphoglycerate kinase 1 (PGK1)
Code: EC 2.7.2.3
Organism: Homo Sapiens
Classification: transferase
Structural weight: 90282.72
Sequence status: incomplete
Annotation
• Catalyzes the formation of ATP to ADP and vice versa. In the
second step of the second phase in glycolysis, 1,3bisphosphoglycerate is converted to 3-phosphoglycerate,
forming one molecule of ATP. This reaction is essential in
most cells for the generation of ATP in aerobes, for
fermentation in anaerobes and for carbon fixation in plants.
• Catalytic activity:
3-phospho-D-glycerate + ATP = 3-phospho-D-glyceroyl phosphate
+ ADP
Pic 1 – Graphic reaction
Substrates
• 3-Phosphoglyceric acid (3PG) is a biochemically significant
3-carbon molecule that is a metabolic intermediate in both
glycolysis and the Calvin cycle.
Pic 2 – Strucrure of
3-Phosphoglyceric acid
Pic 3 – A 3D-balls diagram of
3-Phosphoglyceric acid
Substrates
Adenosine-5'-triphosphate (ATP)
Pic 4 – Strucrure of ATP
Pic 5 – A 3D-balls diagram of ATP
Pic 6 – LIGPLOT of interactions involving ligand
Structure of PGK1
Pic 7 – Secondary structure
Structure of PGK1
Pic 8 – Globular structure
Pic 9 – A skeleton diagram
Pic 10 – A space filling diagram
Is it useful?
Disease relevance of PGK1
• Hypoxic treatment of various mouse and human hepatoma cell lines led to
the expected increase in the amount of PGK1 and PKM2 mRNA, while
HIF-1alpha mRNA levels were not significantly elevated.
• The human phosphoglycerate kinase (PGK1) gene is located within Xq11Xq13, a region implicated in familial prostate carcinoma, androgen
insensitivity, perineal hypospadias, and other genitourinary abnormalities.
• Phosphoglycerate kinase (PGK) deficiency is associated with hereditary
haemolytic anaemia and often with central nervous system dysfunction
and/or myopathy .
• Use of cultured lymphoblastoid cells for the study of abnormal enzymes:
molecular abnormality of a phosphoglycerate kinase variant associated with
hemolytic anemia.
Analytical, diagnostic and therapeutic context of PGK1
• Allele sizes were measured with an automated DNA sequencer after
polymerase chain reaction (PCR) based copying of the PGK1 STR region.
• The Southern blot and PCR assay gave similar results with regards to the
PGK gene.
• The structural abnormality of the phosphoglycerate kinase variant, PGK
München, associated with red cell enzyme deficiency and heat instability,
was elucidated by a microscale peptide-mapping method.
Methods
• PCR;
• Amplification;
• Cloning;
Publications
Pic 11 – Publications from Gopubmed
World map
Pic 12 – Worldmap from Gopubmed
Universities and academies
1. Institute of Enzymology, Hungarian Academy
of Sciences
2. Beckman Research Institute of the City of
Hope, California
3. Shinshu University School of Medicine,
Matsumoto, Japan
4. Université Catholique de Louvain, Brussels,
Belgium
5. Université de Paris-Sud, Orsay, France
References
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Expression of hypoxia-inducible genes in tumor cells. Kress, S., Stein, A., Maurer, P.,
Weber, B., Reichert, J., Buchmann, A., Huppert, P., Schwarz, M. J. Cancer Res. Clin. Oncol.
(1998)
Short tandem repeat polymorphism linkage to the androgen receptor gene in prostate
carcinoma. Riley, D.E., Krieger, J.N. Cancer (2001)
Other erythrocyte enzyme deficiencies associated with non-haematological symptoms:
phosphoglycerate kinase and phosphofructokinase deficiency. Fujii, H., Miwa, S.
Baillière's best practice & research. Clinical haematology. (2000)
Use of cultured lymphoblastoid cells for the study of abnormal enzymes: molecular
abnormality of a phosphoglycerate kinase variant associated with hemolytic anemia.
Fujii, H., Chen, S.H., Akatsuka, J., Miwa, S., Yoshida, A. Proc. Natl. Acad. Sci. U.S.A.
(1981)
A single amino acid substitution (157 Gly----Val) in a phosphoglycerate kinase variant
(PGK Shizuoka) associated with chronic hemolysis and myoglobinuria. Fujii, H.,
Kanno, H., Hirono, A., Shiomura, T., Miwa, S. Blood (1992)
Identification of new mutations in two phosphoglycerate kinase (PGK) variants
expressing different clinical syndromes: PGK Créteil and PGK Amiens. Cohen-Solal,
M., Valentin, C., Plassa, F., Guillemin, G., Danze, F., Jaisson, F., Rosa, R. Blood (1994)
Other references
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www.gopubmed.org
www.pdb.org
www.uniprot.org/uniprot/P00558
http://www.ebi.ac.uk/pdbsum/3c39