Sandbox Reserved 1165: Difference between revisions

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Research for class B GCGR [https://en.wikipedia.org/wiki/Enzyme_inhibitor inhibitors] is primarily looking into [https://en.wikipedia.org/wiki/Allosteric_regulation allosteric inhibitors] having the ability to target specific receptors in order to treat problems like [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> Known inhibitors include [https://en.wikipedia.org/wiki/Monoclonal_antibody monoclonal antibodies] which inhibit glucagon receptors through an allosteric mechanism. The monoclonal antibodies bind to two different sites, the ECD opposite of the binding region and then the helical portion of the ECD as well. <ref name="Last">PMID: 19305799</ref>

===Research===

Determining the structure of class B GCGRs is a reason for its lack of advanced knowledge in the field, but [https://en.wikipedia.org/wiki/X-ray_crystallography X-ray crystallography] and [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance NMR] have been the main processes performed and have had some success with it over the past couple years <ref name="Lastt">PMID: 26227798</ref>. X-ray crystallography displayed the [https://en.wikipedia.org/wiki/Crystal_structure crystal structure] of ECDs of class B GPCRs in complex with their [https://en.wikipedia.org/wiki/Ligand ligands] along with the crystal structure of the 7TM. In addition to this, NMR has allowed the ability to directly understand structures of soluble amino-terminal domains of numerous members of the secretin-like family that bind [https://en.wikipedia.org/wiki/Peptide_hormone peptide hormones]. Primary sequences analysis have led to the finding of seven segments of eighteen or more relatively hydrophobic residues that are believed to represent transmembrane helices that take part in creating an intramembranous helical bundle <ref name="Lastt">PMID: 26227798</ref>. Also, [https://en.wikipedia.org/wiki/Mutagenesis mutagenesis] has been used to determine which residues were necessary in maximizing affinity for glucagon. Finally, the orientation and mechanism of the peptide interactions within these structures are studied using peptide structure-activity relationships (SAR), receptor and ligand fragments, chimeric receptors, site-directed mutagenesis, photochemical cross-linking, and molecular modeling <ref name="Lastt">PMID: 26227798</ref>.

Determining the structure of class B GCGRs is a reason for its lack of advanced knowledge in the field, but [https://en.wikipedia.org/wiki/X-ray_crystallography X-ray crystallography] and [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance NMR] have been the main processes performed and have had some success with it over the past couple years. <ref name="Lastt">PMID: 26227798</ref> X-ray crystallography displayed the [https://en.wikipedia.org/wiki/Crystal_structure crystal structure] of ECDs of class B GPCRs in complex with their [https://en.wikipedia.org/wiki/Ligand ligands] along with the crystal structure of the 7TM. In addition to this, NMR has allowed the ability to directly understand structures of soluble amino-terminal domains of numerous members of the secretin-like family that bind [https://en.wikipedia.org/wiki/Peptide_hormone peptide hormones]. Primary sequences analysis have led to the finding of seven segments of eighteen or more relatively hydrophobic residues that are believed to represent transmembrane helices that take part in creating an intramembranous helical bundle. <ref name="Lastt">PMID: 26227798</ref> Also, [https://en.wikipedia.org/wiki/Mutagenesis mutagenesis] has been used to determine which residues were necessary in maximizing affinity for glucagon. Finally, the orientation and mechanism of the peptide interactions within these structures are studied using peptide structure-activity relationships (SAR), receptor and ligand fragments, chimeric receptors, site-directed mutagenesis, photochemical cross-linking, and molecular modeling. <ref name="Lastt">PMID: 26227798</ref>

</StructureSection>

Sandbox Reserved 1165: Difference between revisions

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@@ Line 40: / Line 40: @@
 Research for class B GCGR [https://en.wikipedia.org/wiki/Enzyme_inhibitor inhibitors] is primarily looking into [https://en.wikipedia.org/wiki/Allosteric_regulation allosteric inhibitors] having the ability to target specific receptors in order to treat problems like [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> Known inhibitors include [https://en.wikipedia.org/wiki/Monoclonal_antibody monoclonal antibodies] which inhibit glucagon receptors through an allosteric mechanism. The monoclonal antibodies bind to two different sites, the ECD opposite of the binding region and then the helical portion of the ECD as well. <ref name="Last">PMID: 19305799</ref>
 ===Research===
-Determining the structure of class B GCGRs is a reason for its lack of advanced knowledge in the field, but [https://en.wikipedia.org/wiki/X-ray_crystallography X-ray crystallography] and [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance NMR] have been the main processes performed and have had some success with it over the past couple years <ref name="Lastt">PMID: 26227798</ref>. X-ray crystallography displayed the [https://en.wikipedia.org/wiki/Crystal_structure crystal structure] of ECDs of class B GPCRs in complex with their [https://en.wikipedia.org/wiki/Ligand ligands] along with the crystal structure of the 7TM. In addition to this, NMR has allowed the ability to directly understand structures of soluble amino-terminal domains of numerous members of the secretin-like family that bind [https://en.wikipedia.org/wiki/Peptide_hormone peptide hormones]. Primary sequences analysis have led to the finding of seven segments of eighteen or more relatively hydrophobic residues that are believed to represent transmembrane helices that take part in creating an intramembranous helical bundle <ref name="Lastt">PMID: 26227798</ref>. Also, [https://en.wikipedia.org/wiki/Mutagenesis mutagenesis] has been used to determine which residues were necessary in maximizing affinity for glucagon. Finally, the orientation and mechanism of the peptide interactions within these structures are studied using peptide structure-activity relationships (SAR), receptor and ligand fragments, chimeric receptors, site-directed mutagenesis, photochemical cross-linking, and molecular modeling <ref name="Lastt">PMID: 26227798</ref>.
+Determining the structure of class B GCGRs is a reason for its lack of advanced knowledge in the field, but [https://en.wikipedia.org/wiki/X-ray_crystallography X-ray crystallography] and [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance NMR] have been the main processes performed and have had some success with it over the past couple years. <ref name="Lastt">PMID: 26227798</ref> X-ray crystallography displayed the [https://en.wikipedia.org/wiki/Crystal_structure crystal structure] of ECDs of class B GPCRs in complex with their [https://en.wikipedia.org/wiki/Ligand ligands] along with the crystal structure of the 7TM. In addition to this, NMR has allowed the ability to directly understand structures of soluble amino-terminal domains of numerous members of the secretin-like family that bind [https://en.wikipedia.org/wiki/Peptide_hormone peptide hormones]. Primary sequences analysis have led to the finding of seven segments of eighteen or more relatively hydrophobic residues that are believed to represent transmembrane helices that take part in creating an intramembranous helical bundle. <ref name="Lastt">PMID: 26227798</ref> Also, [https://en.wikipedia.org/wiki/Mutagenesis mutagenesis] has been used to determine which residues were necessary in maximizing affinity for glucagon. Finally, the orientation and mechanism of the peptide interactions within these structures are studied using peptide structure-activity relationships (SAR), receptor and ligand fragments, chimeric receptors, site-directed mutagenesis, photochemical cross-linking, and molecular modeling. <ref name="Lastt">PMID: 26227798</ref>
 </StructureSection>