User:Cameron Evans/Sandbox 1: Difference between revisions

Line 82:

Also unlike prokarytoic GluDH, Mammalian GluDH is allosterically controlled by GTP (-), ATP (-), GDP(+) and ADP(+), among other agents that are not likely used in a cell's natural process.<ref name=1hwxyz />

It is thought that there is one large region responsible for the binding of allosteric inhibitors between the catalytic core and the hinge region located...

~~...~~

====Nucleotides====

It is thought that the allosteric inhibitors act as a doorstop to lock GluDH in a closed position and increase product affinity. On the other hand, allosteric regulators are thought to keep GluDH in the open conformation, decreasing product affinity.

It is thought that GTP causes negative allosteric regulation of GluDH by increasing the enzyme's affinity for the product to the extent that the release of the product is the rate limiting step of the overall reaction.

When the enzyme is highly saturated, the enzyme has been found to form an "abortive complex" that is the cofactor and the reagent locked in a non-catalytic conformation. Upon the binding of a positive regulator, like GDP or ADP, the reaction is allowed ~~to go~~ to completion. ADP has also been shown to decrease the affinity of the enzyme to its products.

When the enzyme is highly saturated, the enzyme has been found to form an "abortive complex" that is the cofactor and the reagent locked in a non-catalytic conformation. Upon the binding of a positive regulator, like GDP or ADP, the protein is thought to be forced into the open conformation, driving the reaction is allowed to completion. ADP has also been shown to decrease the affinity of the enzyme to its products.

<scene name='User:Cameron_Evans/Sandbox_1/Gtp_spot_on_hwx/1'>GTP is bound ~~within its pocket~~</scene> via hydrogen bonding. Most of the contacts are with the triphosphate moeity - the sidechains of H209, H450, Y262, R217, R265, R261 - however, the sidechains of K281 and E292 make specific contacts with the adenosine ring (to the carbonyl and the N1 imino, respectively) and S213 makes contact with the 2' hydroxyl on the sugar. The guanidinium of R261 is thought to stack against the purine ring. ADP is thought to bind in a similar way as GTP and ADP have been found to bind antagonistically in competitive studies. <ref name=1hwxyz />

<scene name='User:Cameron_Evans/Sandbox_1/Gtp_spot_on_hwx/1'>GTP is bound</scene> via hydrogen bonding. Most of the contacts are with the triphosphate moeity - the sidechains of H209, H450, Y262, R217, R265, R261 - however, the sidechains of K281 and E292 make specific contacts with the adenosine ring (to the carbonyl and the N1 imino, respectively) and S213 makes contact with the 2' hydroxyl on the sugar. The guanidinium of R261 is thought to stack against the purine ring. ADP is thought to bind in a similar way as GTP and ADP have been found to bind antagonistically in competitive studies. <ref name=1hwxyz />

~~...~~

====Dinucleotides====

The coenzyme is ~~thought to~~ also to bind allosterically in the same region the other allosteric regulators bind.

The NAD(P)(H) coenzyme is has also been shown to bind allosterically in the same region the other allosteric regulators bind.

During reductive amination, NADPH is an inhibitor at pH 8, but not at pH7. Furthermore, NADPH binding is greatly enhanced in the presence of glutamate, where it inhibits the enzyme; however, the enhanced binding observed in the presence of ketoglutarate is not coupled with inhibition.

@@ Line 82: / Line 82: @@
 Also unlike prokarytoic GluDH, Mammalian GluDH is allosterically controlled by GTP (-), ATP (-), GDP(+) and ADP(+), among other agents that are not likely used in a cell's natural process.<ref name=1hwxyz />
 It is thought that there is one large region responsible for the binding of allosteric inhibitors between the catalytic core and the hinge region located...
-...
+====Nucleotides====
 It is thought that the allosteric inhibitors act as a doorstop to lock GluDH in a closed position and increase product affinity. On the other hand, allosteric regulators are thought to keep GluDH in the open conformation, decreasing product affinity.
 It is thought that GTP causes negative allosteric regulation of GluDH by increasing the enzyme's affinity for the product to the extent that the release of the product is the rate limiting step of the overall reaction.
-When the enzyme is highly saturated, the enzyme has been found to form an "abortive complex" that is the cofactor and the reagent locked in a non-catalytic conformation. Upon the binding of a positive regulator, like GDP or ADP, the reaction is allowed to go to completion. ADP has also been shown to decrease the affinity of the enzyme to its products.
+When the enzyme is highly saturated, the enzyme has been found to form an "abortive complex" that is the cofactor and the reagent locked in a non-catalytic conformation. Upon the binding of a positive regulator, like GDP or ADP, the protein is thought to be forced into the open conformation, driving the reaction is allowed to completion. ADP has also been shown to decrease the affinity of the enzyme to its products.
-<scene name='User:Cameron_Evans/Sandbox_1/Gtp_spot_on_hwx/1'>GTP is bound within its pocket</scene> via hydrogen bonding. Most of the contacts are with the triphosphate moeity - the sidechains of H209, H450, Y262, R217, R265, R261 - however, the sidechains of K281 and E292 make specific contacts with the adenosine ring (to the carbonyl and the N1 imino, respectively) and S213 makes contact with the 2' hydroxyl on the sugar. The guanidinium of R261 is thought to stack against the purine ring. ADP is thought to bind in a similar way as GTP and ADP have been found to bind antagonistically in competitive studies. <ref name=1hwxyz />
+<scene name='User:Cameron_Evans/Sandbox_1/Gtp_spot_on_hwx/1'>GTP is bound</scene> via hydrogen bonding. Most of the contacts are with the triphosphate moeity - the sidechains of H209, H450, Y262, R217, R265, R261 - however, the sidechains of K281 and E292 make specific contacts with the adenosine ring (to the carbonyl and the N1 imino, respectively) and S213 makes contact with the 2' hydroxyl on the sugar. The guanidinium of R261 is thought to stack against the purine ring. ADP is thought to bind in a similar way as GTP and ADP have been found to bind antagonistically in competitive studies. <ref name=1hwxyz />
-...
+====Dinucleotides====
-The coenzyme is thought to also to bind allosterically in the same region the other allosteric regulators bind.
+The NAD(P)(H) coenzyme is has also been shown to bind allosterically in the same region the other allosteric regulators bind.
 During reductive amination, NADPH is an inhibitor at pH 8, but not at pH7. Furthermore, NADPH binding is greatly enhanced in the presence of glutamate, where it inhibits the enzyme; however, the enhanced binding observed in the presence of ketoglutarate is not coupled with inhibition.