Structural highlights
Function
TPA1_YEAST Part of a messenger ribonucleoprotein (mRNP) complex at the 3'-UTR of mRNAs. It associates specifically with components of the translation termination complex and is involved in both translation termination and in regulation of normal mRNA decay through translation termination-coupled poly(A) shortening.[1]
Publication Abstract from PubMed
Post-translational ribosomal protein hydroxylation is catalyzed by 2-oxoglutarate (2OG) and ferrous iron dependent oxygenases, and occurs in prokaryotes and eukaryotes. OGFOD1 catalyzes trans-3 prolyl hydroxylation at Pro62 of the small ribosomal subunit protein uS12 (RPS23) and is conserved from yeasts to humans. We describe crystal structures of the human uS12 prolyl 3-hydroxylase (OGFOD1) and its homolog from Saccharomyces cerevisiae (Tpa1p): OGFOD1 in complex with the broad-spectrum 2OG oxygenase inhibitors; N-oxalylglycine (NOG) and pyridine-2,4-dicarboxylate (2,4-PDCA) to 2.1 and 2.6 A resolution, respectively; and Tpa1p in complex with NOG, 2,4-PDCA, and 1-chloro-4-hydroxyisoquinoline-3-carbonylglycine (a more selective prolyl hydroxylase inhibitor) to 2.8, 1.9, and 1.9 A resolution, respectively. Comparison of uS12 hydroxylase structures with those of other prolyl hydroxylases, including the human hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs), reveals differences between the prolyl 3- and prolyl 4-hydroxylase active sites, which can be exploited for developing selective inhibitors of the different subfamilies.
Structure of the Ribosomal Oxygenase OGFOD1 Provides Insights into the Regio- and Stereoselectivity of Prolyl Hydroxylases.,Horita S, Scotti JS, Thinnes C, Mottaghi-Taromsari YS, Thalhammer A, Ge W, Aik W, Loenarz C, Schofield CJ, McDonough MA Structure. 2015 Feb 19. pii: S0969-2126(15)00038-6. doi:, 10.1016/j.str.2015.01.014. PMID:25728928[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Keeling KM, Salas-Marco J, Osherovich LZ, Bedwell DM. Tpa1p is part of an mRNP complex that influences translation termination, mRNA deadenylation, and mRNA turnover in Saccharomyces cerevisiae. Mol Cell Biol. 2006 Jul;26(14):5237-48. PMID:16809762 doi:26/14/5237
- ↑ Horita S, Scotti JS, Thinnes C, Mottaghi-Taromsari YS, Thalhammer A, Ge W, Aik W, Loenarz C, Schofield CJ, McDonough MA. Structure of the Ribosomal Oxygenase OGFOD1 Provides Insights into the Regio- and Stereoselectivity of Prolyl Hydroxylases. Structure. 2015 Feb 19. pii: S0969-2126(15)00038-6. doi:, 10.1016/j.str.2015.01.014. PMID:25728928 doi:http://dx.doi.org/10.1016/j.str.2015.01.014
