Anthony Noles Sandbox: Difference between revisions

Substrate-free aconitase contains a [4Fe-4S]²⁺ 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 H2O molecule. His167 is also hydrogen bonded to the bound H2O in the [4Fe-4S] cluster. Both <scene name='Anthony_Noles_Sandbox/His_101_and_167/2'>His101 and His167</scene> are paired with carboxylates (<scene name='Anthony_Noles_Sandbox/Asp100_and_glu262/2'>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/Ser642/3'>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.