User:Matthew J Lowry/Sandbox 1: Difference between revisions

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Montelukast has the chemical formula of C<sub>35</sub>H<sub>36</sub>ClNO<sub>3</sub>S with a molecular weight of 586.187 Da <ref name="five">https://www3.rcsb.org/ligand/MTK</ref>. The primary target for Montelukast is Cysteinyl Leukotriene Receptor 1 (CysLTR1) which contains 337 amino acids with a molecular weight of 38,541 Da <ref name="six">http://www.uniprot.org/uniprot/Q9Y271#sequences</ref>. It has 4 extracellular domains, 4 cytoplasmic domains, and 7 helical transmembrane domains <ref name="seven">http://www.rcsb.org/pdb/protein/Q9Y271</ref>. Because no three-dimensional model was found for this protein on the PDB, Bandaru, S., et al used a multitude of programs to predict the structure of the protein <ref name="eight">Bandaru, S., Marri, V. K., Kasera, P., Kovuri, P., Girdhar, A., Mittal, D. R., . . . Nayarisseri, A. (2014). Structure based virtual screening of ligands to identify cysteinyl leukotriene receptor 1 antagonist. Bioinformation, 10(10), 652-657. doi:10.6026/97320630010652</ref>. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248348/figure/F1/ Figure 1] of their paper provides an image of their prediction. Though this provides a model for the CysLTR1 protein there is still no model for the complexing of Montelukast with its target protein.
Montelukast has the chemical formula of C<sub>35</sub>H<sub>36</sub>ClNO<sub>3</sub>S with a molecular weight of 586.187 Da <ref name="five">https://www3.rcsb.org/ligand/MTK</ref>. The primary target for Montelukast is Cysteinyl Leukotriene Receptor 1 (CysLTR1) which contains 337 amino acids with a molecular weight of 38,541 Da <ref name="six">http://www.uniprot.org/uniprot/Q9Y271#sequences</ref>. It has 4 extracellular domains, 4 cytoplasmic domains, and 7 helical transmembrane domains <ref name="seven">http://www.rcsb.org/pdb/protein/Q9Y271</ref>. Because no three-dimensional model was found for this protein on the PDB, Bandaru, S., et al used a multitude of programs to predict the structure of the protein <ref name="eight">Bandaru, S., Marri, V. K., Kasera, P., Kovuri, P., Girdhar, A., Mittal, D. R., . . . Nayarisseri, A. (2014). Structure based virtual screening of ligands to identify cysteinyl leukotriene receptor 1 antagonist. Bioinformation, 10(10), 652-657. doi:10.6026/97320630010652</ref>. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248348/figure/F1/ Figure 1] of their paper provides an image of their prediction. Though this provides a model for the CysLTR1 protein there is still no model for the complexing of Montelukast with its target protein.


Montelukast, like any drug, can also bind to non-target proteins. One of these proteins is Cytochrome P450 2C8 (CYP2C8)(<scene name='74/745011/Initial/1'>2NNI-MTK</scene>). This protein is made of 490 amino acids and has a molecular weight of 55,825 Da <ref name="nine">http://www.uniprot.org/uniprot/P10632#sequences</ref>. The peptide chain of Cytochrome P450 2C8 consists of 51% alpha helices and 9% beta sheets<ref name="ten">Kabsch, W., & Sander, C. (1983, December). Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features. Biopolymers, 22(12), 2577-2637. doi:10.1002/bip.360221211</ref>. The structure was determined using the method of X-ray diffraction with a resolution of 2.8 Angstroms<ref name="eleven"> http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nni</ref>. Montelukast (“MTK” scene zoom) is held in place in the active site of CYP2C8 by hydrogen bonds between the side chain of Ser100 and the oxygens carboxyl group of Montelukast (resonance allows H-bond to either oxygens), and Val296 and the tertiary alcohol in Montelukast<ref name="twelve">http://cdn.rcsb.org//poseview/NN/2NNI/MTK/2NNI_MTK.png</ref>. Residue Thr107 helps stabilize the polarity induced by the Chlorine <ref name="twelve"/>. Hydrophobic interactions from amino acids like Alanine, Isoleucine, and Phenylalanine throughout the active site also help stabilize the interaction <ref name="twelve"/>. The binding pocket can be three-dimensionally visualized using [http://www.rcsb.org/pdb/explore/jmol.do?structureId=2NNI&residueNr=MTK JSmol].
Montelukast, like any drug, can also bind to non-target proteins. One of these proteins is Cytochrome P450 2C8 (CYP2C8). This protein is made of 490 amino acids and has a molecular weight of 55,825 Da <ref name="nine">http://www.uniprot.org/uniprot/P10632#sequences</ref>. The peptide chain of Cytochrome P450 2C8 consists of 51% alpha helices and 9% beta sheets<ref name="ten">Kabsch, W., & Sander, C. (1983, December). Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features. Biopolymers, 22(12), 2577-2637. doi:10.1002/bip.360221211</ref>. The structure was determined using the method of X-ray diffraction with a resolution of 2.8 Angstroms<ref name="eleven"> http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nni</ref>. Montelukast (<scene name='74/745011/Initial/2'>MTK</scene>) is held in place in the active site of CYP2C8 by hydrogen bonds between the side chain of Ser100 and the oxygens carboxyl group of Montelukast (resonance allows H-bond to either oxygens), and Val296 and the tertiary alcohol in Montelukast<ref name="twelve">http://cdn.rcsb.org//poseview/NN/2NNI/MTK/2NNI_MTK.png</ref>. Residue Thr107 helps stabilize the polarity induced by the Chlorine <ref name="twelve"/>. Hydrophobic interactions from amino acids like Alanine, Isoleucine, and Phenylalanine throughout the active site also help stabilize the interaction <ref name="twelve"/>. The binding pocket can be three-dimensionally visualized using [http://www.rcsb.org/pdb/explore/jmol.do?structureId=2NNI&residueNr=MTK JSmol].


This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
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