Sandbox Reserved 1168: Difference between revisions

<StructureSection load='4GRV2.pdb' size='340' frame= 'true' align='right' caption='Neurotensin G-Protein Coupled Receptor (PDB Codes [http://www.rcsb.org/pdb/explore/explore.do?structureId=4GRV 4GRV] and [http://www.rcsb.org/pdb/explore/explore.do?structureId=4XEE 4XEE])' scene='72/727765/Overall_structure/2'/>

<scene name='72/721539/Nts8_13/1'>Neurotensin(NTS)</scene> is a 13-amino acid peptide originally isolated from bovine hypothalamus. It fulfills the role of both a neurotransmitter and a neuromodulator in the nervous system and a hormone in the periphery. NTS is a neuromodulator of dopamine transmission and of anterior pituitary hormone secretion. It is also a paracrine and endocrine modulator in the periphery of the digestive tract and cardiovascular system. Finally, NTS serves as a growth factor for many normal and cancerous cell types.(Vincent)

 

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Binding of NTS to the binding site is enriched by <scene name='72/721539/Binding_pocket_surface/3'>charge complementarity</scene> between the positive NTS arginine side chains and the electronegative pocket. In addition, the C-terminus forms a <scene name='72/721539/Binding_site_charges/2'>salt bridge</scene> with R328. Only three out of eight hydrogen bonds are made between the side chains of NTS and the receptor. Most of the interactions are van der Waals interactions. The binding pocket is partially capped by a hairpin loop at the proximal end of the receptor protein's N-terminus. (White)

 

Conserved across all class A GPCRs, a sodium ion-binding pocket is seen in the middle of TM2 helix. The ion is coordinated with a highly conserved D^2.50 and four other contacts with oxygen atoms. Some of these oxygen atoms are sourced from water molecules. In order for G-protein activation, a hydrogen bond network with T^3.39, S^7.46 ,N^7.49 of the NPxxY motif, prevents the coordination of a Na⁺.