Аконитаза ферментінің құрылымы мен қатысы

Class of enzymes

Aconitase (aconitate hydratase; ) is an enzyme that catalyses the stereo specific isomerization of citrate to isocitrate via cis aconitate in the tricarboxylic acid cycle, a non redox active process.

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. In the inactive form, its structure is divided into four domains. 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. The iron sulfur cluster is highly sensitive to oxidation by superoxide.

Aconitase employs a dehydration hydration mechanism. His 101 protonates the hydroxyl group on C3 of citrate, allowing it to leave as water, and Ser 642 concurrently abstracts the proton on C2, creating a double bond between C2 and C3, and forming the so called cis aconitate intermediate (the two carboxyl groups on the double bond are cis). The carbon atom from which the hydrogen is removed is the one that came from oxaloacetate in the previous step of the citric acid cycle, not the one that came from acetyl CoA, even though these two carbons are equivalent except that one is "pro R" and the other "pro S" (see Prochirality). At this point, the intermediate is rotated 180°. Because of this flip, the intermediate is said to move from a "citrate mode" to a "isocitrate mode." How exactly this flip occurs is debatable. One theory is that, in the rate limiting step of the mechanism, the cis aconitate is released from the enzyme, then reattached in the isocitrate mode to complete the reaction. Another hypothesis is that cis aconitate stays bound to the enzyme while it flips from the citrate to the isocitrate mode. In either case, flipping cis aconitate allows the dehydration and hydration steps to occur on opposite faces of the intermediate. Aconitase catalyzes trans elimination/addition of water, and the flip guarantees that the correct stereochemistry is formed in the product. 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.

Aconitases are expressed in bacteria to humans. Humans express the following two aconitase isozymes: