User:Mark Macbeth/Sandbox7: Difference between revisions

From Proteopedia
Jump to navigationJump to search
No edit summary
No edit summary
 
Line 24: Line 24:


== Mechanism of Action==
== Mechanism of Action==
[[Image:LSD1Mechanism.png|700 px|right|thumb|Figure 3: Hydride transfer mechanism of LSD-1 active site via FAD cofactor.]]
[[Image:LSD_1_Chemdraw_Real.png|700 px|right|thumb|Figure 3: Hydride transfer mechanism of LSD-1 active site via FAD cofactor.]]


The mechanism of lysine demethylation is highly dependent on the presence of the <scene name='81/811089/Fadcofactor/4'>FAD cofactor</scene>. The FAD cofactor, positioned closely to the substrate lysine in the active site, acts as an oxidizing agent and initiates catalysis (Figure 3). A two-electron transfer occurs between the substrate lysine and FAD in the form of a [https://en.wikipedia.org/wiki/Hydride hydride]; the lysine is oxidized and the FAD is reduced <ref name="Stavropolous"/>. The FAD cofactor forms an anion and is stabilized by the positively charged <scene name='81/811088/Lys661/3'>Lys661</scene> positioned in the catalytic pocket of the active site <ref name="Stavropolous"/>. The oxidized lysine forms an aminium cation that is hydrolyzed into the carbinolamine intermediate <ref name="Stavropolous"/>. The carbinolamine intermediate readily decomposes into formaldehyde and the demethylated lysine substrate <ref name="Stavropolous"/>.
The mechanism of lysine demethylation is highly dependent on the presence of the <scene name='81/811089/Fadcofactor/4'>FAD cofactor</scene>. The FAD cofactor, positioned closely to the substrate lysine in the active site, acts as an oxidizing agent and initiates catalysis (Figure 3). A two-electron transfer occurs between the substrate lysine and FAD in the form of a [https://en.wikipedia.org/wiki/Hydride hydride]; the lysine is oxidized and the FAD is reduced <ref name="Stavropolous"/>. The FAD cofactor forms an anion and is stabilized by the positively charged <scene name='81/811088/Lys661/3'>Lys661</scene> positioned in the catalytic pocket of the active site <ref name="Stavropolous"/>. The oxidized lysine forms an aminium cation that is hydrolyzed into the carbinolamine intermediate <ref name="Stavropolous"/>. The carbinolamine intermediate readily decomposes into formaldehyde and the demethylated lysine substrate <ref name="Stavropolous"/>.