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| | ==Crystal structure of Tpa1p from Saccharomyces cerevisiae, termination and polyadenylation protein 1, in complex with N-[(1-chloro-4-hydroxyisoquinolin-3-yl)carbonyl]glycine (IOX3/UN9)== | | ==Crystal structure of Tpa1p from Saccharomyces cerevisiae, termination and polyadenylation protein 1, in complex with N-[(1-chloro-4-hydroxyisoquinolin-3-yl)carbonyl]glycine (IOX3/UN9)== |
| - | <StructureSection load='4nhm' size='340' side='right' caption='[[4nhm]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='4nhm' size='340' side='right'caption='[[4nhm]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4nhm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NHM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NHM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4nhm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NHM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NHM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=UN9:N-[(1-CHLORO-4-HYDROXYISOQUINOLIN-3-YL)CARBONYL]GLYCINE'>UN9</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nhl|4nhl]], [[4nhk|4nhk]], [[4nhx|4nhx]], [[4nhy|4nhy]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=UN9:N-[(1-CHLORO-4-HYDROXYISOQUINOLIN-3-YL)CARBONYL]GLYCINE'>UN9</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TPA1, YER049W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4nhm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nhm OCA], [https://pdbe.org/4nhm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nhm RCSB], [https://www.ebi.ac.uk/pdbsum/4nhm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nhm ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4nhm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nhm OCA], [http://pdbe.org/4nhm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nhm RCSB], [http://www.ebi.ac.uk/pdbsum/4nhm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nhm ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TPA1_YEAST 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.<ref>PMID:16809762</ref> | + | [https://www.uniprot.org/uniprot/TPA1_YEAST 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.<ref>PMID:16809762</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Baker's yeast]] | + | [[Category: Large Structures]] |
| - | [[Category: McDonough, M A]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Schofield, C J]] | + | [[Category: McDonough MA]] |
| - | [[Category: Scotti, J S]] | + | [[Category: Schofield CJ]] |
| - | [[Category: 2-oxoglutarate oxygenase]] | + | [[Category: Scotti JS]] |
| - | [[Category: Double-stranded beta helix]]
| + | |
| - | [[Category: Jellyroll fold]]
| + | |
| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
| + | |
| - | [[Category: Oxygen sensing]]
| + | |
| - | [[Category: Prolyl hydroxylase]]
| + | |
| - | [[Category: Protein synthesis regulation]]
| + | |
| - | [[Category: Ribosome]]
| + | |
| - | [[Category: Translation]]
| + | |
| 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
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