Aconitase
aconitate hydratase | |||||||||
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KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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Aconitase family (aconitate hydratase) | |||||||||
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Aconitase (aconitate hydratase;
Structure
Aconitase, displayed in the structures in the right margin of this page, has two slightly different structures, depending on whether it is activated or inactivated.
4 anion also reside in the active site.[6] When the enzyme is activated, it gains an additional iron atom, creating a [4Fe-4S] cluster.[7][8] However, the structure of the rest of the enzyme is nearly unchanged; the conserved atoms between the two forms are in essentially the same positions, up to a difference of 0.1 angstroms.[7]
Function
In contrast with the majority of
The
Aconitase is inhibited by fluoroacetate, therefore fluoroacetate is poisonous. Fluoroacetate, in the citric acid cycle, is converted to fluorocitrate by citrate synthase. Fluorocitrate competitively inhibits aconitase halting the citric acid cycle.[9] The iron sulfur cluster is highly sensitive to oxidation by superoxide.[10]
Mechanism
Aconitase employs a dehydration-hydration mechanism.
How exactly this flip occurs is debatable. One theory is that, in the
In either case, flipping cis-aconitate allows the dehydration and hydration steps to occur on opposite faces of the intermediate.[11] Aconitase catalyzes trans elimination/addition of water, and the flip guarantees that the correct stereochemistry is formed in the product.[11][12] To complete the reaction, the serine and histidine residues reverse their original catalytic actions: the histidine, now basic, abstracts a proton from water, priming it as a nucleophile to attack at C2, and the protonated serine is deprotonated by the cis-aconitate double bond to complete the hydration, producing isocitrate.[11]
Family members
Aconitases are expressed in bacteria to humans. Humans express the following two aconitase isozymes:
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Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- ^ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78".
References
- PMID 1547214.
- PMID 8151704.
- S2CID 1107246.
- PMID 11848829.
- PMID 11848830.
- ^ S2CID 36219029.
- ^ PMID 2726740.
- PMID 1547214.
- PMID 13208639.
- PMID 11912933.
- ^ a b c d e f g h i Takusagawa F. "Chapter 16: Citric Acid Cycle" (PDF). Takusagawa’s Note. The University of Kansas. Archived from the original (PDF) on 2012-03-24. Retrieved 2011-07-10.
- ^ PMID 11848830. Archived from the original(PDF) on 2011-08-11. Retrieved 2011-05-16.
- ^ PMID 10631981.
- PMID 16142896.
- Biochemistry(2nd ed.). pp. 295–296.
- ^ S2CID 43006515.
- ^ "Aconitase family". The Prosthetic groups and Metal Ions in Protein Active Sites Database Version 2.0. The University of Leeds. 1999-02-02. Archived from the original on 2011-06-08. Retrieved 2011-07-10.
Further reading
- Frishman D, Hentze MW (Jul 1996). "Conservation of aconitase residues revealed by multiple sequence analysis. Implications for structure/function relationships". European Journal of Biochemistry. 239 (1): 197–200. PMID 8706708.
External links
- Aconitase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Proteopedia Aconitase - the Aconitase structure in interactive 3D