Sandbox Reserved 1706: Difference between revisions

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Arg1276 is the critical residue within the GRD site needed for proper binding to Ras. The interaction between <scene name='90/904312/Arg_1276_open/10'>Arg1276 and Ras in the open conformation</scene>

<scene name='90/904312/Arg_1276_open/11'>(zoomed in)</scene> is only possible in the open confirmation (Figure #). In the open confirmation, the arginine finger binds to the backbone gamma carbon of Y32 to assist in eventual hydrolysis of GTP. In the closed conformation this was inhibited by E31 but in the open conformation the conformational change allows for an interaction of R1276 and the gamma carbon so they align with one another. This allows for the normal function of NF1 in the rapid rate increase of GTP hydrolysis upon Ras binding.

<scene name='90/904312/Closed_arg/1'>Arg1276 in closed conformation</scene> ~~has~~ <scene name='90/904312/Closed_zoom/1'>steric clashing with Ras</scene> making binding of Ras impossible (Figure #). In the closed confirmation the Arginine finger attempts to bind the backbone gamma carbon(~~Ras~~) of a Tyrosine residue(Y32) to assist in hydrolysis, but instead clashes with a Glutamate residue(E31) that would otherwise not interfere in the open conformation and can no longer bind properly. This residue impacts binding of Ras and is of critical importance in determining if Ras is able to bind to the GRD site or not to assist in eventual hydrolysis of GTP.

<scene name='90/904312/Closed_arg/1'>Arg1276 in closed conformation has</scene>

<scene name='90/904312/Closed_zoom/1'>steric clashing with Ras</scene> making binding of Ras impossible (Figure #). In the closed confirmation the Arginine finger attempts to bind the backbone gamma carbon(RAS) of a Tyrosine residue(Y32) to assist in hydrolysis, but instead clashes with a Glutamate residue(E31) that would otherwise not interfere in the open conformation and can no longer bind properly. This residue impacts binding of Ras and is of critical importance in determining if Ras is able to bind to the GRD site or not to assist in eventual hydrolysis of GTP.

Mutations to the arginine finger are shown to slow function of NF1 and other GTPases in their function in accelerating GTP hydrolysis. When a Ras GAP such as NF1 can functionally utilize its arginine finger, it allows NF1 to rapidly hydrolyze GTP when bound to Ras. This emphasizes the importance of the R1276 residue for the GRD site binding to Ras.

==SPRED 1==

Sandbox Reserved 1706: Difference between revisions

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@@ Line 38: / Line 38: @@
 Arg1276 is the critical residue within the GRD site needed for proper binding to Ras. The interaction between <scene name='90/904312/Arg_1276_open/10'>Arg1276 and Ras in the open conformation</scene>
 <scene name='90/904312/Arg_1276_open/11'>(zoomed in)</scene> is only possible in the open confirmation (Figure #).  In the open confirmation, the arginine finger binds to the backbone gamma carbon of Y32 to assist in eventual hydrolysis of GTP. In the closed conformation this was inhibited by E31 but in the open conformation the conformational change allows for an interaction of R1276 and the gamma carbon so they align with one another. This allows for the normal function of NF1 in the rapid rate increase of GTP hydrolysis upon Ras binding.
- <scene name='90/904312/Closed_arg/1'>Arg1276 in closed conformation</scene> has <scene name='90/904312/Closed_zoom/1'>steric clashing with Ras</scene> making binding of Ras impossible (Figure #). In the closed confirmation the Arginine finger attempts to bind the backbone gamma carbon(Ras) of a Tyrosine residue(Y32) to assist in hydrolysis, but instead clashes with a Glutamate residue(E31) that would otherwise not interfere in the open conformation and can no longer bind properly. This residue impacts binding of Ras and is of critical importance in determining if Ras is able to bind to the GRD site or not to assist in eventual hydrolysis of GTP.
+<scene name='90/904312/Closed_arg/1'>Arg1276 in closed conformation has</scene>
+<scene name='90/904312/Closed_zoom/1'>steric clashing with Ras</scene> making binding of Ras impossible (Figure #). In the closed confirmation the Arginine finger attempts to bind the backbone gamma carbon(RAS) of a Tyrosine residue(Y32) to assist in hydrolysis, but instead clashes with a Glutamate residue(E31) that would otherwise not interfere in the open conformation and can no longer bind properly. This residue impacts binding of Ras and is of critical importance in determining if Ras is able to bind to the GRD site or not to assist in eventual hydrolysis of GTP.
 Mutations to the arginine finger are shown to slow function of NF1 and other GTPases in their function in accelerating GTP hydrolysis. When a Ras GAP such as NF1 can functionally utilize its arginine finger, it allows NF1 to rapidly hydrolyze GTP when bound to Ras. This emphasizes the importance of the R1276 residue for the GRD site binding to Ras.
 ==SPRED 1==