Systematic analysis of NO Regular Secondary structural regions (NORS) in membrane and non-membrane proteins

Saravanan, Konda Mani; Peng, Yin; Wei, Yanjie

doi:10.1080/07391102.2019.1566092

Cited by 3 publications

(3 citation statements)

References 13 publications

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“…1 Although these receptors typically have seven transmembrane helices, they show vast sequence variations, especially in loop regions and perform various physiological functions. [2][3][4][5][6][7] The seven transmembrane helices are embedded in the membrane, and small molecular ligands from the extracellular domain of receptor 8 activate the protein.…”

Section: Introductionmentioning

confidence: 99%

“…Guanine protein coupled receptors (GPCR) is one of the largest group of membrane receptors in eukaryotes which plays critical roles in signaling 1 . Although these receptors typically have seven transmembrane helices, they show vast sequence variations, especially in loop regions and perform various physiological functions 2–7 . The seven transmembrane helices are embedded in the membrane, and small molecular ligands from the extracellular domain of receptor 8 activate the protein.…”

Section: Introductionmentioning

confidence: 99%

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Structural analysis of human G‐protein‐coupled receptor 17 ligand binding sites

Mani

Ramesh

Yli‐Harja

et al. 2023

J of Cellular Biochemistry

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The human G protein coupled membrane receptor (GPR17), the sensor of brain damage, is identified as a biomarker for many neurological diseases. In human brain tissue, GPR17 exist in two isoforms, long and short. While cryo‐electron microscopy technology has provided the structure of the long isoform of GPR17 with Gi complex, the structure of the short isoform and its activation mechanism remains unclear. Recently, we theoretically modeled the structure of the short isoform of GPR17 with Gi signaling protein and identified novel ligands. In the present work, we demonstrated the presence of two distinct ligand binding sites in the short isoform of GPR17. The molecular docking of GPR17 with endogenous (UDP) and synthetic ligands (T0510.3657, MDL29950) found the presence of two distinct binding pockets. Our observations revealed that endogenous ligand UDP can bind stronger in two different binding pockets as evidenced by glide and autodock vina scores, whereas the other two ligand's binding with GPR17 has less docking score. The analysis of receptor−UDP interactions shows complexes' stability in the lipid environment by 100 ns atomic molecular dynamics simulations. The amino acid residues VAL83, ARG87, and PHE111 constitute ligand binding site 1, whereas site 2 constitutes ASN67, ARG129, and LYS232. Root mean square fluctuation analysis showed the residues 83, 87, and 232 with higher fluctuations during molecular dynamics simulation in both binding pockets. Our findings imply that the residues of GPR17's two binding sites are crucial, and their interaction with UDP reveals the protein's hidden signaling and communication properties. Furthermore, this finding may assist in the development of targeted therapies for the treatment of neurological diseases.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structural analysis of human G‐protein‐coupled receptor 17 ligand binding sites

Mani

Ramesh

Yli‐Harja

et al. 2023

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…Furthermore, this approach ultimately leaves macrocycles that engage in non-regular secondary structures (NORS) without adequate options for conformational description. 35–37 A comprehensive approach to evaluating macrocyclic peptide conformation must be established to meet these challenges.…”

Section: Introductionmentioning

confidence: 99%