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Protein Hydroxylation Catalyzed by 2-Oxoglutarate-dependent Oxygenases.

Markolovic S, Wilkins SE, Schofield CJ - J. Biol. Chem. (2015)

Bottom Line: Subsequently, they have been shown to catalyze N-demethylation (via hydroxylation) of N(ϵ)-methylated histone lysyl residues, as well as hydroxylation of multiple other residues.Recent work has identified roles for 2OG oxygenases in the modification of translation-associated proteins, which in some cases appears to be conserved from microorganisms through to humans.Here we give an overview of protein hydroxylation catalyzed by 2OG oxygenases, focusing on recent discoveries.

View Article: PubMed Central - PubMed

Affiliation: From the Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, United Kingdom.

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2OG oxygenases involved in protein synthesis. 2OG oxygenases catalyze hydroxylation and demethylation reactions that regulate transcriptional, post-transcriptional, translational, and post-translational processes. The names of enzymes that catalyze hydroxylation are in bold. ALKBH, alkylated DNA repair protein alkB homolog; TET1–3, ten-eleven translocation 1–3; FTO, fat mass- and obesity-associated protein; TYW5, tRNA wybutosine-synthesizing protein 5; C-P4Hs, collagen prolyl 4-hydroxylases; C-P3Hs, collagen prolyl 3-hydroxylases; PLODs, pro-collagen lysine 2-oxoglutarate 5-dioxygenase enzymes; P4HTM, transmembrane prolyl 4-hydroxylase.
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Figure 3: 2OG oxygenases involved in protein synthesis. 2OG oxygenases catalyze hydroxylation and demethylation reactions that regulate transcriptional, post-transcriptional, translational, and post-translational processes. The names of enzymes that catalyze hydroxylation are in bold. ALKBH, alkylated DNA repair protein alkB homolog; TET1–3, ten-eleven translocation 1–3; FTO, fat mass- and obesity-associated protein; TYW5, tRNA wybutosine-synthesizing protein 5; C-P4Hs, collagen prolyl 4-hydroxylases; C-P3Hs, collagen prolyl 3-hydroxylases; PLODs, pro-collagen lysine 2-oxoglutarate 5-dioxygenase enzymes; P4HTM, transmembrane prolyl 4-hydroxylase.

Mentions: The past 15 years have seen major advances in our understanding of the extent of 2OG oxygenase-catalyzed modifications to proteins. We now know that such modifications are likely common in all eukaryotes and in many prokaryotes, but not archaea. 2OG oxygenase-catalyzed post-translational modifications to proteins, along with related modifications to nucleic acids, are involved in all stages of protein biosynthesis in animals (Fig. 3). Although controversies remain and much work is still to be done, one can start to envisage how combined biochemical and cellular approaches will lead to the assignment of molecular functions for all human 2OG oxygenases, i.e. defining the reactions they catalyze and the substrate(s) that they accept. However, for only a few of the identified modifications are the cellular roles linked to physiology. Notably, these include the pioneering discoveries of collagen C-4 prolyl hydroxylation, HIF-α prolyl hydroxylation, and in some cases, histone demethylation. Future work, guided by genetic analyses, can now be focused on this objective.


Protein Hydroxylation Catalyzed by 2-Oxoglutarate-dependent Oxygenases.

Markolovic S, Wilkins SE, Schofield CJ - J. Biol. Chem. (2015)

2OG oxygenases involved in protein synthesis. 2OG oxygenases catalyze hydroxylation and demethylation reactions that regulate transcriptional, post-transcriptional, translational, and post-translational processes. The names of enzymes that catalyze hydroxylation are in bold. ALKBH, alkylated DNA repair protein alkB homolog; TET1–3, ten-eleven translocation 1–3; FTO, fat mass- and obesity-associated protein; TYW5, tRNA wybutosine-synthesizing protein 5; C-P4Hs, collagen prolyl 4-hydroxylases; C-P3Hs, collagen prolyl 3-hydroxylases; PLODs, pro-collagen lysine 2-oxoglutarate 5-dioxygenase enzymes; P4HTM, transmembrane prolyl 4-hydroxylase.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4543633&req=5

Figure 3: 2OG oxygenases involved in protein synthesis. 2OG oxygenases catalyze hydroxylation and demethylation reactions that regulate transcriptional, post-transcriptional, translational, and post-translational processes. The names of enzymes that catalyze hydroxylation are in bold. ALKBH, alkylated DNA repair protein alkB homolog; TET1–3, ten-eleven translocation 1–3; FTO, fat mass- and obesity-associated protein; TYW5, tRNA wybutosine-synthesizing protein 5; C-P4Hs, collagen prolyl 4-hydroxylases; C-P3Hs, collagen prolyl 3-hydroxylases; PLODs, pro-collagen lysine 2-oxoglutarate 5-dioxygenase enzymes; P4HTM, transmembrane prolyl 4-hydroxylase.
Mentions: The past 15 years have seen major advances in our understanding of the extent of 2OG oxygenase-catalyzed modifications to proteins. We now know that such modifications are likely common in all eukaryotes and in many prokaryotes, but not archaea. 2OG oxygenase-catalyzed post-translational modifications to proteins, along with related modifications to nucleic acids, are involved in all stages of protein biosynthesis in animals (Fig. 3). Although controversies remain and much work is still to be done, one can start to envisage how combined biochemical and cellular approaches will lead to the assignment of molecular functions for all human 2OG oxygenases, i.e. defining the reactions they catalyze and the substrate(s) that they accept. However, for only a few of the identified modifications are the cellular roles linked to physiology. Notably, these include the pioneering discoveries of collagen C-4 prolyl hydroxylation, HIF-α prolyl hydroxylation, and in some cases, histone demethylation. Future work, guided by genetic analyses, can now be focused on this objective.

Bottom Line: Subsequently, they have been shown to catalyze N-demethylation (via hydroxylation) of N(ϵ)-methylated histone lysyl residues, as well as hydroxylation of multiple other residues.Recent work has identified roles for 2OG oxygenases in the modification of translation-associated proteins, which in some cases appears to be conserved from microorganisms through to humans.Here we give an overview of protein hydroxylation catalyzed by 2OG oxygenases, focusing on recent discoveries.

View Article: PubMed Central - PubMed

Affiliation: From the Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, United Kingdom.

Show MeSH
Related in: MedlinePlus