Aconitase: Difference between revisions
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Michal Harel (talk | contribs) No edit summary |
removing extra bonds in FeS cluster, as explained in the Talk page; changed scenes 7acn-morph/ 3 and 4 |
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== Catalytic mechanism of mitochondrial ACO == | == Catalytic mechanism of mitochondrial ACO == | ||
Both mAc and cAc are quite similar in their ACO function. Studies, however, concentrated on <scene name='Aconitase/7acn-sf4/1'>the mitochondrial ACO</scene>. ACO is an excellent system for understanding the role of iron-sulfur-clusters in catalysis. The <scene name='Aconitase/7acn-sf4/2'>(4Fe-4S) cofactor is held in place</scene> by three sulfur atoms belonging to the cysteins-385, -448, and -451 <scene name=' | Both mAc and cAc are quite similar in their ACO function. Studies, however, concentrated on <scene name='Aconitase/7acn-sf4/1'>the mitochondrial ACO</scene>. ACO is an excellent system for understanding the role of iron-sulfur-clusters in catalysis. The <scene name='Aconitase/7acn-sf4/2'>(4Fe-4S) cofactor is held in place</scene> by three sulfur atoms belonging to the cysteins-385, -448, and -451 <scene name='33/338089/7acn-morph/5'>which are bound to three of the four</scene> cluster iron atoms. On activation of the enzyme, <scene name='33/338089/7acn-morph/6'>a fourth iron atom is included in the cluster</scene> together with a water molecule.This Fe4 is free to bind one, two, or three partners, in this reaction always oxygen atoms belonging to other molecules.<ref>PMID:8151704</ref> | ||
<!--It is clear that, in order to synthesize L-isocitrate, stereoselective catalysis must occur.--> | <!--It is clear that, in order to synthesize L-isocitrate, stereoselective catalysis must occur.--> | ||
Substrate-free aconitase contains a [4Fe-4S]<sup>2+</sup> cluster with hydroxyl bound to one of the Fe. Upon binding of substrate the bound hydroxyl is protonated. A hydrogen bond from <scene name='Anthony_Noles_Sandbox/His101/3'>His101</scene> to the isocitrate hydroxyl is donated to form water. Alternatively, the proton could be donated by <scene name='Anthony_Noles_Sandbox/His167/3'>His167</scene> as this histidine is hydrogen bonded to a H<sub>2</sub>O molecule. His167 is also hydrogen bonded to the bound H<sub>2</sub>O in the [4Fe-4S] cluster. Both <scene name='Anthony_Noles_Sandbox/His_101_and_167/4'>His101 and His167</scene> are paired with carboxylates (<scene name='Anthony_Noles_Sandbox/Asp100_and_glu262/3'>Asp100 and Glu262</scene>, respectively) and are likely to be protonated. The conformational change associated with substrate binding reorients the cluster. <ref name="Beinert" /> The residue which removes a proton from citrate or isocitrate is <scene name='Anthony_Noles_Sandbox/Ser642/4'>Ser642</scene>. <ref name="Beinert" /> This causes the cis-Aconitate intermediate (seen below), which consists of a double bond, which is a direct result of the deprotonation. Then, there is a rehydration of the double bond of cis-aconitate to form isocitrate (if the original substrate was citrate). To better understand this, consider this process as stages, seen below. | Substrate-free aconitase contains a [4Fe-4S]<sup>2+</sup> cluster with hydroxyl bound to one of the Fe. Upon binding of substrate the bound hydroxyl is protonated. A hydrogen bond from <scene name='Anthony_Noles_Sandbox/His101/3'>His101</scene> to the isocitrate hydroxyl is donated to form water. Alternatively, the proton could be donated by <scene name='Anthony_Noles_Sandbox/His167/3'>His167</scene> as this histidine is hydrogen bonded to a H<sub>2</sub>O molecule. His167 is also hydrogen bonded to the bound H<sub>2</sub>O in the [4Fe-4S] cluster. Both <scene name='Anthony_Noles_Sandbox/His_101_and_167/4'>His101 and His167</scene> are paired with carboxylates (<scene name='Anthony_Noles_Sandbox/Asp100_and_glu262/3'>Asp100 and Glu262</scene>, respectively) and are likely to be protonated. The conformational change associated with substrate binding reorients the cluster. <ref name="Beinert" /> The residue which removes a proton from citrate or isocitrate is <scene name='Anthony_Noles_Sandbox/Ser642/4'>Ser642</scene>. <ref name="Beinert" /> This causes the cis-Aconitate intermediate (seen below), which consists of a double bond, which is a direct result of the deprotonation. Then, there is a rehydration of the double bond of cis-aconitate to form isocitrate (if the original substrate was citrate). To better understand this, consider this process as stages, seen below. | ||
