Pyruvate synthase
pyruvate synthase | |||||||||
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ExPASy NiceZyme view | | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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In
the interconversion of pyruvate and acetyl-CoA. It is also called pyruvate:ferredoxin oxidoreductase (PFOR).The relevant equilibrium catalysed by PFOR is:
- pyruvate + CoA + oxidized ferredoxin acetyl-CoA + CO2 + reduced ferredoxin
The 3
, and reduced ferredoxin.Function
This enzyme participates in 4
Its major role is the extraction of reducing equivalents by the decarboxylation. In aerobic organisms, this conversion is catalysed by pyruvate dehydrogenase, also uses
Nomenclature
This enzyme belongs to the family of oxidoreductases, specifically those acting on the aldehyde or oxo group of donor with an iron-sulfur protein as acceptor.[1] The systematic name of this enzyme class is pyruvate:ferredoxin 2-oxidoreductase (CoA-acetylating). Other names in common use include:
- pyruvate oxidoreductase,
- pyruvate synthetase,
- pyruvate:ferredoxin oxidoreductase,
- pyruvic-ferredoxin oxidoreductase.
Structure
PFOR adopts a dimeric structure, while each monomeric subunit is composed of one or multiple chain(s) of polypeptides.
Catalytic Mechanism
An PFOR reaction starts with the nucleophilic attack of C2 of TPP on the 2-oxo carbon of pyruvate, which forms a lactyl-TPP adduct. Next, the lactyl-TPP adduct releases the CO2 moiety, forming an anionic intermediate, which then transfer an electron to a [4Fe-4S] cluster. These steps lead to a stable radical intermediate that can be observed by electron paramagnetic resonance (EPR) experiments. The radical intermediate reacts with a CoA molecule, transfers another electron from the radical intermediate to a [4Fe-4S] cluster and forms an acetyl-CoA product.[3]
Inhibitors
- broad-spectrum antiparasitic drug and FDA-approved PFOR inhibitor which is used for the treatment of Giardiasis and Cryptosporidiosis.[4][5]
- Tizoxanide, an active metabolite of nitazoxanide
References
- ^ PMID 27315560.
- PMID 29581263.
- PMID 12797832.
- PMID 24202339.
Nitazoxanide [NTZ: 2-acetyloxy-N-(5-nitro-2-thiazolyl)benzamide] is a thiazolide antiparasitic agent with excellent activity against a wide variety of protozoa and helminths. ... Nitazoxanide (NTZ) is a main compound of a class of broad-spectrum anti-parasitic compounds named thiazolides. It is composed of a nitrothiazole-ring and a salicylic acid moiety which are linked together by an amide bond ... NTZ is generally well tolerated, and no significant adverse events have been noted in human trials [13]. ... In vitro, NTZ and tizoxanide function against a wide range of organisms, including the protozoal species Blastocystis hominis, C. parvum, Entamoeba histolytica, G. lamblia and Trichomonas vaginalis [13]
- ^ "Nitazoxanide Prescribing Information" (PDF). United States Food and Drug Administration. Romark Pharmaceuticals. 3 March 2004. pp. 1–9. Retrieved 3 January 2016.
- PMID 22585229.
- PMID 24890599.
Further reading
- Evans MC, Buchanan BB (1965). "Photoreduction of ferredoxin and its use in carbon dioxide fixation by a subcellular system from a photosynthetic bacterium". Proc. Natl. Acad. Sci. U.S.A. 53 (6): 1420–5. PMID 5217644.
- Gehring U, Arnon DI (1972). "Purification and properties of -ketoglutarate synthase from a photosynthetic bacterium". J. Biol. Chem. 247 (21): 6963–9. PMID 4628267.
- Uyeda K, Rabinowitz JC (1971). "Pyruvate-ferredoxin oxidoreductase. 3. Purification and properties of the enzyme". J. Biol. Chem. 246 (10): 3111–9. PMID 5574389.
- Uyeda K, Rabinowitz JC (1971). "Pyruvate-ferredoxin oxidoreductase. IV. Studies on the reaction mechanism". J. Biol. Chem. 246 (10): 3120–5. PMID 4324891.
- Charon MH, Volbeda A, Chabriere E, Pieulle L, Fontecilla-Camps JC (1999). "Structure and electron transfer mechanism of pyruvate:ferredoxin oxidoreductase". Curr. Opin. Struct. Biol. 9 (6): 663–9. PMID 10607667.