4NHL: Crystal structure of Tpa1p from Saccharomyces cerevisiae, termination and polyadenylation protein 1, in complex with N-oxalylglycine (NOG)

Citation:
Abstract
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.
PDB ID: 4NHLDownload
MMDB ID: 124827
PDB Deposition Date: 2013/11/5
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 2.84  Å
Source Organism:
Similar Structures:
Biological Unit for 4NHL: monomeric; determined by author and by software (PISA)
Molecular Components in 4NHL
Label Count Molecule
Protein (1 molecule)
1
Pkhd-type Hydroxylase Tpa1(Gene symbol: TPA1)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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