Sandbox Reserved 425
From Proteopedia
| Line 25: | Line 25: | ||
===Binding Interactions=== | ===Binding Interactions=== | ||
<Structure load='2zvj' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | <Structure load='2zvj' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | ||
| - | Met 40, Leu 198, and Tyr 200 define the pocket for the 4-phenyl-7, 8-dihydroxycoumarine (4PCM) | + | Met 40, Leu 198, and Tyr 200 define the pocket for the 4-phenyl-7, 8-dihydroxycoumarine (4PCM) ligand binding site. Trp 38 and Pro 174 make Van der Waals interactions with the 4PCM. The magnesium ion interacts with the two hydroxyl groups of the 4PCM. The magnesium ion also aids in the protonation of Lys 144, causing an electrostatic interaction with a hydroxyl group of 4PCM. The other end of this Lys 144 then acts a hydrogen bond donor for a water molecule in the binding pocket. This water molecule then acts a hydrogen bond donor for the carbonyl group of 4PCM, creating an interesting network of hydrogen bonds. The above interactions stabilize the ligand in the binding pocket. These interactions are somewhat similar to other inhibitors previously used, however some differences do occur that make past inhibitors more stable. In our 4PCM, we can see a bond angle between the sulfur and carbon atoms of Met 40 to be significantly less than that of the Met 40 in a COMT complex using <scene name='Sandbox_Reserved_425/3_5-dinitrocatchetol/1'>3,5-dinitrocatchetol</scene> as an inhibitor instead; the change is about 96o. |
Revision as of 03:48, 17 April 2012
|
| This Sandbox is Reserved from January 19, 2016, through August 31, 2016 for use for Proteopedia Team Projects by the class Chemistry 423 Biochemistry for Chemists taught by Lynmarie K Thompson at University of Massachusetts Amherst, USA. This reservation includes Sandbox Reserved 425 through Sandbox Reserved 439. |
Contents |
YourMacromolecule
Introduction
- COMT responsible for degradation of catchol neurotransmitters including DA
- PD symptoms result from low levels of DA
- inhibiting COMT has potential to treat PD in conjunction with L-DOPA (a DA precursor currently used to treat PD) by increasing the bioavailability and stability of L-DOPA
- 4PCM is a COMT inhibitor being studied to better understand inhibitor interactions with COMT in order to develop better inhibitors
- carbonyl oxygen of 4PCM interacts with
Overall Structure
-beta sheets-kinds-how many-locations
Binding Interactions
|
Met 40, Leu 198, and Tyr 200 define the pocket for the 4-phenyl-7, 8-dihydroxycoumarine (4PCM) ligand binding site. Trp 38 and Pro 174 make Van der Waals interactions with the 4PCM. The magnesium ion interacts with the two hydroxyl groups of the 4PCM. The magnesium ion also aids in the protonation of Lys 144, causing an electrostatic interaction with a hydroxyl group of 4PCM. The other end of this Lys 144 then acts a hydrogen bond donor for a water molecule in the binding pocket. This water molecule then acts a hydrogen bond donor for the carbonyl group of 4PCM, creating an interesting network of hydrogen bonds. The above interactions stabilize the ligand in the binding pocket. These interactions are somewhat similar to other inhibitors previously used, however some differences do occur that make past inhibitors more stable. In our 4PCM, we can see a bond angle between the sulfur and carbon atoms of Met 40 to be significantly less than that of the Met 40 in a COMT complex using as an inhibitor instead; the change is about 96o.
Additional Features
Other health condition that relates to COMT gene.
22q11.2 deletion syndrome is associated with the COMT gene.
-22q11.2 deletion syndrome is a deletion of a small piece of chromosome 22.
-chromosomal region that was deleted contains 30 to 40 genes including the COMT gene
As a result of the deletion:
- people who has this disorder have only one copy of the COMT gene in each cell
-A loss of one copy of the COMT gene in each cell leads to abnormal regulation of catechol-O-methyltransferase levels in the brain
-People with 22q11.2 deletion syndrome are more likely to develop one of these syndrome: schizophrenia, depression, anxiety, and bipolar disorder.
Variations in the COMT gene:
- mental illness in people without 22q11.2 deletion syndrome.
- the risk of developing schizophrenia
-the effects of a particular common variation (polymorphism) in catechol-O-methyltransferase
Credits
Introduction - Jessica Royal
Overall Structure - Stephanie Bristol
Drug Binding Site - Emily Brackett
Additional Features - Anh Huynh
