Sandbox Reserved 425
From Proteopedia
(→Additional Features) |
(→Additional Features) |
||
| Line 49: | Line 49: | ||
-22q11.2 deletion syndrome is a deletion of a small piece of chromosome 22. | -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: | As a result of the deletion: | ||
| + | |||
- people who has this disorder have only one copy of the COMT gene in each cell | - 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 | -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. | -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: | Variations in the COMT gene: | ||
| + | |||
- mental illness in people without 22q11.2 deletion syndrome. | - mental illness in people without 22q11.2 deletion syndrome. | ||
| + | |||
- the risk of developing schizophrenia | - the risk of developing schizophrenia | ||
| + | |||
-the effects of a particular common variation (polymorphism) in catechol-O-methyltransferase | -the effects of a particular common variation (polymorphism) in catechol-O-methyltransferase | ||
Revision as of 19:59, 10 March 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
Biological Unit with DNA - green scene
Polar/nonpolar regions green scene
Secondary Structure green scene
-alpha helixes-phi and psi angles in one helix-how many-location
-beta sheets-kinds-how many-locations
Ligand structure KOM-AC3, MG-AC1, SAM-AC2 ball and stick green scene
Binding Interactions
Met 40, Leu 198, Tyr 200, Trp 38, and Pro 174 pocket for 4-phenyl-7, 8-dihydroxycoumarine (4PCM) These are mostly hydrophobic interactions. Van der Waals interactions with these molecules, especially M40, and hydrogen bonds between W48 and K144 stabilize 4PCM. P174 restricts 4PCM mobility and limits interactions with the COMT protein. These stabilizing residues and evolutionarily conserved.
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
