Sandbox Reserved 1165: Difference between revisions
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[[Image:Screen_Shot_2016-03-22_at_5.28.03_PM.png|(|):|425 px|center|thumb|'''Figure 3: Binding Pocket Residues:''' Residues with side chains of carbon(utilizing the [https://en.wikipedia.org/wiki/Hydrophobic_effect hydrophobic effect]) are shown in green and side chains containing oxygen ([https://en.wikipedia.org/wiki/Hydrophile hydrophilic]) are shown in red. The properties of hydrophobicity and hydrophilicity of the residues create the [https://en.wikipedia.org/wiki/Ligand_%28biochemistry%29#Receptor.2Fligand_binding_affinity binding affinity] of glucagon.<ref name="Ligands">PMID: 21542831</ref> This image depicts the open conformation of GCGR.]] | [[Image:Screen_Shot_2016-03-22_at_5.28.03_PM.png|(|):|425 px|center|thumb|'''Figure 3: Binding Pocket Residues:''' Residues with side chains of carbon(utilizing the [https://en.wikipedia.org/wiki/Hydrophobic_effect hydrophobic effect]) are shown in green and side chains containing oxygen ([https://en.wikipedia.org/wiki/Hydrophile hydrophilic]) are shown in red. The properties of hydrophobicity and hydrophilicity of the residues create the [https://en.wikipedia.org/wiki/Ligand_%28biochemistry%29#Receptor.2Fligand_binding_affinity binding affinity] of glucagon.<ref name="Ligands">PMID: 21542831</ref> This image depicts the open conformation of GCGR.]] | ||
The [https://en.wikipedia.org/wiki/Residue_(chemistry) residues] in the binding pocket that are in direct contact with the glucagon molecule are [https://en.wikipedia.org/wiki/Chemical_polarity polar] (utilizing the attraction of opposite charges or | The [https://en.wikipedia.org/wiki/Residue_(chemistry) residues] in the binding pocket that are in direct contact with the glucagon molecule are [https://en.wikipedia.org/wiki/Chemical_polarity polar] (utilizing the attraction of opposite charges or [https://en.wikipedia.org/wiki/Dipole dipoles] for glucagon binding) or are hydrophobic (utilizing the hydrophobic effect). The [https://en.wikipedia.org/wiki/Active_site binding site] location of the hormone peptide ligand has been identified, and the N-terminus of glucagon is known to bind partly with the ECD while the rest of glucagon binds deep into the binding pocket (Figure 3). The [https://en.wikipedia.org/wiki/Amino_acid amino acids] at the N-terminus of the class B 7TM have the ability to form [https://en.wikipedia.org/wiki/Hydrogen_bond hydrogen bonds] and [https://en.wikipedia.org/wiki/Ionic_bonding ionic interactions], which can be seen in the [https://en.wikipedia.org/wiki/Peptide_sequence amino acid sequence] of glucagon (Figure 4). <ref name="Sequence">PMID: 11946536</ref> | ||
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=Clinical Relevancy= | =Clinical Relevancy= | ||
Of the fifteen human class B GPCRs, eight have been confirmed as potential [https://en.wikipedia.org/wiki/Biological_target drug target]. <ref name="Drug">PMID: 24628305</ref> However, overall family B | Of the fifteen human class B GPCRs, eight have been confirmed as potential [https://en.wikipedia.org/wiki/Biological_target drug target]. <ref name="Drug">PMID: 24628305</ref> However, overall family B GPCRs have been difficult drug targets. This difficulty is partially related to the inherent flexibility in the class B GCGR 7TM. The flexibility comes from the ability of GCGR to be a receptor many ligands. The GCGR's interactions on the extracellular side of the receptor may provide evidence to how class B receptors adjust the conformational spectra for various ligands. Researchers hope to show how these conformations can be utilized in potential treatments of a wide array [https://en.wikipedia.org/wiki/List_of_mental_disorders disorders]. <ref name="Drug">PMID: 24628305</ref> | ||
=Potential Inhibitors for GCGR= | =Potential Inhibitors for GCGR= | ||
There are potential class B GCGR [https://en.wikipedia.org/wiki/Enzyme_inhibitor inhibitors] that have clinic relevancy. These inhibitors to class B GCGRs have primarily focused on [https://en.wikipedia.org/wiki/Allosteric_regulation allosteric inhibitors] with high specificity and the ability to treat diseases including: [https://en.wikipedia.org/wiki/Stress-related_disorders stress disorders], managing [http://www.webmd.com/diabetes/guide/diabetes-hyperglycemia hyperglycemia], and also alternative mechanisms for treating [https://en.wikipedia.org/wiki/Migraine migraines]. <ref name="Inhibitors">PMID: 24189067</ref> Inhibitors include [https://en.wikipedia.org/wiki/Monoclonal_antibody monoclonal antibodies] which inhibit glucagon receptors through an allosteric mechanism. <ref name="Last">PMID: 19305799</ref> There is further research still to be done on GCGR to determine more inhibitors for clinical relevance. | There are potential class B GCGR [https://en.wikipedia.org/wiki/Enzyme_inhibitor inhibitors] that have clinic relevancy. These inhibitors to class B GCGRs have primarily focused on [https://en.wikipedia.org/wiki/Allosteric_regulation allosteric inhibitors] with high specificity and the ability to treat diseases including: [https://en.wikipedia.org/wiki/Stress-related_disorders stress disorders], managing [http://www.webmd.com/diabetes/guide/diabetes-hyperglycemia hyperglycemia], and also alternative mechanisms for treating [https://en.wikipedia.org/wiki/Migraine migraines]. <ref name="Inhibitors">PMID: 24189067</ref> Inhibitors include [https://en.wikipedia.org/wiki/Monoclonal_antibody monoclonal antibodies] which inhibit glucagon receptors through an allosteric mechanism. <ref name="Last">PMID: 19305799</ref> There is further research still to be done on GCGR to determine more inhibitors for clinical relevance. | ||
