title: Mining human genome for novel purinergic P2Y receptors: a sequence analysis and molecular modeling approach.
abstract: The purinergic P2Y receptors are G-protein coupled receptors (GPCRs) that control many physiological processes by mediating cellular responses to purines, pyrimidines and their analogues. They can be used as potential therapeutic targets in a variety of disease conditions. Therefore, it is critical to identify new members of this family of receptors from the human genome and characterize them for their role in health and disease. In the present work, molecular modeling was carried out for the 21 known P2Y receptors. Binding site analysis was done on the basis of docking and site-directed mutagenesis data. Thus, conserved features of P2Y receptors could be formulated. These features can be used to determine the purinergic nature of potential P2Y receptors in the human genome. We applied this knowledge to human genome GPCR sequences found by sensitive sequence search techniques and identified two orphan receptors, namely GPR34 and GP171 that have all the necessary conserved features of P2Y receptors.
authors.affiliation: Division of Biotechnology, Netaji Subhas Institute of Technology, New Delhi, India. ecc999@gmail.com
authors.forename: Sonika
authors.initials: S
authors.lastname: Bhatnagar
authors.forename: Shubhi
authors.initials: S
authors.lastname: Mishra
authors.forename: Ravi
authors.initials: R
authors.lastname: Pathak
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010710:Phosphates / Q000378:metabolism; D010802:Phylogeny; D058470:Receptors, Purinergic P2Y / Q000737:chemistry* / Q000378:metabolism; D015203:Reproducibility of Results; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D014443:Tyrosine / Q000378:metabolism
chemical_list: D008024:Ligands; D010710:Phosphates; D058470:Receptors, Purinergic P2Y; D014443:Tyrosine; D000255:Adenosine Triphosphate