biochemistry multi-part question and need the explanation and answer to help me learn.
Hi! I receive a feedback for this assignment that “The images do not highlight any interactions between the ligand’s functional groups and the enzyme’s amino acid residues. Many of these images have poor angles, which do not highlight the ligand’s interactions. There is a lack of captions describing the images”. Could you provide the caption for each image to explain what’s shown in the image? and please change the PyMOL image used in “The structure of human MAOA and the comparison with the early known structure” box to one that really display a ligand or inhibitor and with a better angle showing the images. The images showing previously is cluttered
The structure of human MAOA and the comparison with the early known structure A PyMol Images Crystal Structure of Human Monoamine Oxidase A with Harmine Background Being a crucial flavoenzyme in biochemistry, mitochondrial outer membrane-anchored monoamine oxidase (MAO) catalyzes the deamination of biogenic and exogenous amines. Given their connections to many mental conditions, its two variants, MAOA and MAOB, present intriguing targets for medication development. substrate access to the active site. Structure Because Tyr-326 in MAOB and Ile-335 in MAOA have different structural makeups, the inhibitor selectivity of MAOA and MAOB is a result. Similar to rat MAOA, the structures display a C-terminal transmembrane helix with a distinct electron density. Mechanism of Action A mutation in one residue of loop 108–118, G110, which is near the membrane surface but distant from the active centre, results in a sharp decrease in the activity of the solubilized enzyme; however, this effect is mitigated when the enzyme is anchored in the membrane. These findings imply that loop 108–118’s flexibility, which is made possible by the enzyme’s membrane anchoring. Enzyme Structural Mechanism Application of the Enzyme An important class of medications recommended for the treatment of depression and other neurological disorders are monoamine oxidase inhibitors, or MAOIs. There is evidence that patients with atypical depression react more favorably to MAOIs found in natural products. These substances have strong potency, excellent bioavailability, minimal toxicity, and broad-spectrum anti-disease efficacy. While methoxycoumarins have anti-Alzheimer’s disease and antioxidant qualities, natural coumarins are neuroprotective, anti-inflammatory, antidiabetic, antidepressant, and anticonvulsant. References Myburg, T., Petzer, A., & Petzer, J. P. (2022). The inhibition of monoamine oxidase by harmine derivatives. Results in Chemistry, 4, 100607. Manzoor, S., & Hoda, N. (2020). A comprehensive review of monoamine oxidase inhibitors as Anti-Alzheimer’s disease agents: A review. European Journal of Medicinal Chemistry, 206, 112787.
Conclusion In the present research, a number of harmines and related carbazole compounds were synthesized, and their ability to inhibit MAO was examined. The finding that harmine is a potent MAO-A inhibitor served as the foundation for this investigation. Additionally, it has been observed that harmine analogues such 2-methylharminium, 2,9-dimethylharminium, and harmaline function as reversible competitive inhibitors of MAO-A. This published study supports the idea that the efficacy of MAO inhibition is determined by electronic features rather than steric variables. It demonstrates how β-carbolines interact with the FAD to generate spectrum alterations. Future Aspect It is possible to draw the conclusion that the active inhibitors found in this study could provide guidance for the future creation of medications intended to treat neuropsychiatric and neurodegenerative conditions including Parkinson’s disease and depression. Mechanism of Action