Inscriere cercetatori

Premii Ad Astra

premii Ad Astra

Asociația Ad Astra a anunțat câștigătorii Premiilor Ad Astra 2022: Proiectul și-a propus identificarea și popularizarea modelelor de succes, a rezultatelor excepționale ale cercetătorilor români din țară și din afara ei.

Asociatia Ad Astra a cercetatorilor romani lanseaza BAZA DE DATE A CERCETATORILOR ROMANI DIN DIASPORA. Scopul acestei baze de date este aceea de a stimula colaborarea dintre cercetatorii romani de peste hotare dar si cu cercetatorii din Romania. Cercetatorii care doresc sa fie nominalizati in aceasta baza de date sunt rugati sa trimita un email la

Characterization of determinants of ligand binding to the nicotinic acid receptor GPR109A (HM74A/PUMA-G).

Domenii publicaţii > Biologie + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: Tunaru S, Lättig J, Kero J, Krause G, Offermanns S

Editorial: Mol Pharmacol., Nov;68(5), p.1271-80, 2005.


The G-protein-coupled receptor GPR109A (HM74A/PUMA-G) has recently been shown to function as a receptor for nicotinic acid (niacin) and to mediate its antilipolytic effects. Nicotinic acid is able to strongly raise plasma levels of high-density lipoprotein cholesterol, a property that distinguishes nicotinic acid from other lipid-lowering drugs. To investigate the structural determinants of GPR109A ligand binding, we performed site-directed mutagenesis of putative ligand binding residues combined with generation of chimeric receptors consisting of GPR109A and its close relative GPR109B, which does not bind nicotinic acid. We could identify Asn86/Trp91 [transmembrane helix (TMH) 2/extracellular loop (ECL) 1], Arg111 (TMH3), Ser178 (ECL2), Phe276 (TMH7), and Tyr284 (TMH7) as amino acid residues critical for binding of nicotinic acid. Together with data from molecular modeling studies, our data suggest that the ligand binding pocket for nicotinic acid of GPR109A is distinct from that of most other group A receptors. Although Arg111 at TMH3 serves as the basic anchor point for the carboxylate ligands, the ring system of nicotinic acid is embedded between Trp91 at the junction TMH2/ECL1 and Phe276/Tyr284 at TMH7. The heterocyclic ring is also bound to Ser178 at ECL2 via an H-bond. These data will facilitate the design of new antidyslipidemic drugs acting via GPR109A.

Cuvinte cheie: receptor pharmacology, binding site, site-directed mutagenesis