Sandbox Reserved 702: Difference between revisions
From Proteopedia
Jump to navigationJump to search
| Line 118: | Line 118: | ||
The current model for the catalytic reaction of edema factor is the following: the reaction is mediated by the nucleophilic attack of the 3' oxygen atom on the α-phosphate. Indeed, this oxygen in near the α-phosphate. The distance between the nucleophile 3'O and the α-phosphate atom os ATP is shorter than 3.5 Å. A 3'-endo conformation of the ribose and a direct coordination of the 3'O atom by the catalytic magnesium ion is the ideal geometry for the initiation of the nucleophilic attack of the 3'O on the α-phosphate. <ref> PMID: 15719022</ref> | The current model for the catalytic reaction of edema factor is the following: the reaction is mediated by the nucleophilic attack of the 3' oxygen atom on the α-phosphate. Indeed, this oxygen in near the α-phosphate. The distance between the nucleophile 3'O and the α-phosphate atom os ATP is shorter than 3.5 Å. A 3'-endo conformation of the ribose and a direct coordination of the 3'O atom by the catalytic magnesium ion is the ideal geometry for the initiation of the nucleophilic attack of the 3'O on the α-phosphate. <ref> PMID: 15719022</ref> | ||
The [[adenylyl cyclase]] reaction takes place in several steps: binding of ATP to the edema factor, enabling the deprotonation of 3'OH, stabilization of the penta-coordinated phosphorus intermediate and finally the release of cAMP and pyrophosphate. The enzyme binds its substrate, ATP and asparagine 583 | The [[adenylyl cyclase]] reaction takes place in several steps: binding of ATP to the edema factor, enabling the deprotonation of 3'OH, stabilization of the penta-coordinated phosphorus intermediate and finally the release of cAMP and pyrophosphate. The enzyme binds its substrate, ATP and asparagine 583 interacts with it to restrict the rotation of the ribose. 3'OH is so hold in place for its nucleophilic attack during the catalysis. Moreover, the protonated histidine 351 stabilizes the HO- ion near the 3'OH group. Another model is that a neutral histidine deprotonates a water molecule and that the resulting HO- ion facilitates the deprotonation of 3'OH of ATP. <ref> PMID: 15719022</ref> | ||
The magnesium ion that is coordinated by <scene name='Sandbox_Reserved_702/Asp_and_his/2'>aspartates 491 and 493 and histidine 577</scene> is localized near the 3'OH of ATP. Since it is positively charged, it stabilizes the negative charge of the 3'-oxyanion and thus facilitates the deprotonation of 3'OH. The action of this ion and of <scene name='Sandbox_Reserved_702/histidine_351/1'>Histidine 351</scene> can be additive. To summarise, histidine 351 increases the local pH by attracting HO-, and the metal ion decreases the pKa of the 3'OH group. Maybe the magnesium ion also stabilizes the reaction intermediate by moving towards the non-bridging oxygen of α-phosphate durung the nucleophilic attack. <ref> PMID: 15719022</ref> | The magnesium ion that is coordinated by <scene name='Sandbox_Reserved_702/Asp_and_his/2'>aspartates 491 and 493 and histidine 577</scene> is localized near the 3'OH of ATP. Since it is positively charged, it stabilizes the negative charge of the 3'-oxyanion and thus facilitates the deprotonation of 3'OH. The action of this ion and of <scene name='Sandbox_Reserved_702/histidine_351/1'>Histidine 351</scene> can be additive. To summarise, histidine 351 increases the local pH by attracting HO-, and the metal ion decreases the pKa of the 3'OH group. Maybe the magnesium ion also stabilizes the reaction intermediate by moving towards the non-bridging oxygen of α-phosphate durung the nucleophilic attack. <ref> PMID: 15719022</ref> | ||
