PDBsum entry 4ccn

Oxidoreductase

PDB id: 4ccn

Contents

Protein chains

458 a.a.

Ligands

GLY-GLY-ASN-HIS-GLN-HIS-ILE-CYS-LYS-PRO ×2

OGA ×2

SO4 ×2

EDO

Metals

_MN ×2

Waters ×363

PDB id:

4ccn

Name:

Oxidoreductase

Title:

60s ribosomal protein l8 histidine hydroxylase (no66 l299c/c300s) in complex with mn(ii), n-oxalylglycine (nog) and 60s ribosomal protein l8 (rpl8 g220c) peptide fragment (complex-2)

Structure:

Bifunctional lysine-specific demethylase and histidyl- hydroxylase no66. Chain: a, b. Fragment: catalytic domain, residues 183-641. Synonym: 60s ribosomal protein l8 histidine hydroxylase, histone lysine demethylase no66, myc-associated protein with jmjc domain, nucleolar protein 66, hsno66, ribosomal oxygenase no66, rox. Engineered: yes. 60s ribosomal protein l8.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 9606

Resolution:

2.23Å R-factor: 0.238 R-free: 0.248

Authors:

R.Chowdhury,C.J.Schofield

Key ref:

R.Chowdhury et al. (2014). Ribosomal oxygenases are structurally conserved from prokaryotes to humans. Nature, 510, 422-426. PubMed id: 24814345 DOI: 10.1038/nature13263

Date:

23-Oct-13 Release date: 14-May-14

Protein chains

Q9H6W3  (RIOX1_HUMAN) -  Ribosomal oxygenase 1 from Homo sapiens

Seq: 641 a.a.

Struc: 458 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: E.C.1.14.11.27 - [histone H3]-dimethyl-L-lysine(36) demethylase.
• Reaction: N₆,N₆-dimethyl-L-lysyl₃₆-[histone H3] + 2 2-oxoglutarate + 2 O2 = L-lysyl₃₆-[histone H3] + 2 formaldehyde + 2 succinate + 2 CO2
• Cofactor: Fe(2+)
• Enzyme class 3: E.C.1.14.11.79 - protein-L-histidine (3S)-3-hydroxylase.
• Reaction: L-histidyl-[protein] + 2-oxoglutarate + O2 = (3S)-3-hydroxy-L-histidyl- [protein] + succinate + CO2

L-histidyl-[protein] (Bound ligand (Het Group name = GLN) matches with 58.33% similarity) + 2 × 2-oxoglutarate + 2 × O2 = (3S)-3-hydroxy-L-histidyl- [protein] + 2 × succinate (Bound ligand (Het Group name = GLY) matches with 50.00% similarity) + 2 × CO2

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/nature13263

Nature 510:422-426 (2014)

PubMed id: 24814345

Ribosomal oxygenases are structurally conserved from prokaryotes to humans.

R.Chowdhury, R.Sekirnik, N.C.Brissett, T.Krojer, C.H.Ho, S.S.Ng, I.J.Clifton, W.Ge, N.J.Kershaw, G.C.Fox, J.R.Muniz, M.Vollmar, C.Phillips, E.S.Pilka, K.L.Kavanagh, F.von Delft, U.Oppermann, M.A.McDonough, A.J.Doherty, C.J.Schofield.

ABSTRACT

2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components and in the hydroxylation of transcription factors and splicing factor proteins. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA and ribosomal proteins have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone N(ε)-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases.