Sandbox reserved 915: Difference between revisions
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===Inhibition of MGL=== | ===Inhibition of MGL=== | ||
The importance of inhibiting Monoglyceride lipase is to keep it from breaking down 2-arachidonoyl glycerol. When 2-Ag is broken down it is not able to suppress pain and depression brain functions that human beings experience. N-arachidonyl maleimide (NAM) is one inhibitor of MGL that reacts with the amino acid <scene name='58/580298/Cys252/1'>Cys252</scene>. [[Image:NAM.png|thumb|'''Figure 2:''' The structure of N-arachidonyl maleimide (NAM)that interacts with Cys252.]] | The importance of inhibiting Monoglyceride lipase is to keep it from breaking down 2-arachidonoyl glycerol. When 2-Ag is broken down it is not able to suppress pain and depression brain functions that human beings experience. N-arachidonyl maleimide (NAM) is one inhibitor of MGL that reacts with the amino acid <scene name='58/580298/Cys252/1'>Cys252</scene>. | ||
[[Image:NAM.png|thumb|'''Figure 2:''' The structure of N-arachidonyl maleimide (NAM)that interacts with Cys252.]] | |||
This Cysteine is buried in the active site near the catalytic serine and functions by sterically clashing with the natural ligand. A possible conformational change to Cys252 upon the binding of NAM could also lead to an inactive form of MGL. | This Cysteine is buried in the active site near the catalytic serine and functions by sterically clashing with the natural ligand. A possible conformational change to Cys252 upon the binding of NAM could also lead to an inactive form of MGL. | ||
MGL is also inhibited by being in complex with <scene name='58/580298/Sar629/2'>SAR629</scene> that is covalently bound to the catalytic Ser132. SAR629 adopts a Y shape and interacts with the MGL by hydrophobic interactions, with a few polar interactions as well. [[Image:SAR.png|'''Figure 3:''' The structure and shape of SAR629.]] | MGL is also inhibited by being in complex with <scene name='58/580298/Sar629/2'>SAR629</scene> that is covalently bound to the catalytic Ser132. SAR629 adopts a Y shape and interacts with the MGL by hydrophobic interactions, with a few polar interactions as well. | ||
[[Image:SAR.png|thumb|'''Figure 3:''' The structure and shape of SAR629.]] | |||
With SAR629 interacting with the catalytic triad it inhibits the triad from breaking down 2-AG and inactivates MGL <ref name="Bertrand" /> | With SAR629 interacting with the catalytic triad it inhibits the triad from breaking down 2-AG and inactivates MGL <ref name="Bertrand" /> | ||
