Limits...
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.

Show MeSH

Related in: MedlinePlus

Hydroxylations catalyzed by human 2OG oxygenases. Human 2OG oxygenases catalyze the stereoselective hydroxylation of prolyl, lysyl, asparaginyl, aspartyl, and histidinyl residues in protein substrates; the oxygen atom incorporated into the product is shown in red. Note that the stereochemistry of JMJD4-catalyzed hydroxylation is unknown. C-P4Hs, collagen prolyl 4-hydroxylases; C-P3Hs, collagen prolyl 3-hydroxylases; PLODs, pro-collagen lysine 2-oxoglutarate 5-dioxygenase enzymes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4543633&req=5

Figure 2: Hydroxylations catalyzed by human 2OG oxygenases. Human 2OG oxygenases catalyze the stereoselective hydroxylation of prolyl, lysyl, asparaginyl, aspartyl, and histidinyl residues in protein substrates; the oxygen atom incorporated into the product is shown in red. Note that the stereochemistry of JMJD4-catalyzed hydroxylation is unknown. C-P4Hs, collagen prolyl 4-hydroxylases; C-P3Hs, collagen prolyl 3-hydroxylases; PLODs, pro-collagen lysine 2-oxoglutarate 5-dioxygenase enzymes.

Mentions: The JmjC subfamily of 2OG oxygenases contains both hydroxylases, such as FIH, as well as demethylases (51). This dual functionality has led to some controversy in the literature regarding functional assignment, which is well illustrated by the case of JMJD6. JMJD6 (as it is now known) was first assigned as having a key role in apoptosis, acting as a membrane-associated phosphatidyl serine receptor (76, 77). However, this assignment now seems unlikely to be correct; JMJD6 is a 2OG oxygenase that predominantly localizes to the nucleus. JMJD6 was then reported as a 2OG oxygenase acting on N-methylated arginine residues in histone H3, a result that if correct represents the first biochemical evidence for direct removal of arginyl methylation (78). However, subsequent work using NMR and MS analysis of products formed by purified recombinant JMJD6 has shown JMJD6 to be a lysyl C-5 hydroxylase (79); evidence for such activity was also present in an initial report of JMJD6 as an arginyl demethylase (78). Conflicting studies have continued to appear regarding the catalytic activity of JMJD6, leading to the possibility that it has dual functionality. Nonetheless, although we are somewhat biased, there is clear evidence that JMJD6 acts as a lysyl C-5 hydroxylase, interestingly giving the 5S- rather than the 5R- stereochemistry, and thus contrasting with the pro-collagen lysyl hydroxylases (80) (Fig. 2). The evidence for demethylation of N-methylated arginyl residues is much weaker, and there is no evidence for JMJD6 acting as a KDM.


Protein Hydroxylation Catalyzed by 2-Oxoglutarate-dependent Oxygenases.

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

Hydroxylations catalyzed by human 2OG oxygenases. Human 2OG oxygenases catalyze the stereoselective hydroxylation of prolyl, lysyl, asparaginyl, aspartyl, and histidinyl residues in protein substrates; the oxygen atom incorporated into the product is shown in red. Note that the stereochemistry of JMJD4-catalyzed hydroxylation is unknown. C-P4Hs, collagen prolyl 4-hydroxylases; C-P3Hs, collagen prolyl 3-hydroxylases; PLODs, pro-collagen lysine 2-oxoglutarate 5-dioxygenase enzymes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Hydroxylations catalyzed by human 2OG oxygenases. Human 2OG oxygenases catalyze the stereoselective hydroxylation of prolyl, lysyl, asparaginyl, aspartyl, and histidinyl residues in protein substrates; the oxygen atom incorporated into the product is shown in red. Note that the stereochemistry of JMJD4-catalyzed hydroxylation is unknown. C-P4Hs, collagen prolyl 4-hydroxylases; C-P3Hs, collagen prolyl 3-hydroxylases; PLODs, pro-collagen lysine 2-oxoglutarate 5-dioxygenase enzymes.
Mentions: The JmjC subfamily of 2OG oxygenases contains both hydroxylases, such as FIH, as well as demethylases (51). This dual functionality has led to some controversy in the literature regarding functional assignment, which is well illustrated by the case of JMJD6. JMJD6 (as it is now known) was first assigned as having a key role in apoptosis, acting as a membrane-associated phosphatidyl serine receptor (76, 77). However, this assignment now seems unlikely to be correct; JMJD6 is a 2OG oxygenase that predominantly localizes to the nucleus. JMJD6 was then reported as a 2OG oxygenase acting on N-methylated arginine residues in histone H3, a result that if correct represents the first biochemical evidence for direct removal of arginyl methylation (78). However, subsequent work using NMR and MS analysis of products formed by purified recombinant JMJD6 has shown JMJD6 to be a lysyl C-5 hydroxylase (79); evidence for such activity was also present in an initial report of JMJD6 as an arginyl demethylase (78). Conflicting studies have continued to appear regarding the catalytic activity of JMJD6, leading to the possibility that it has dual functionality. Nonetheless, although we are somewhat biased, there is clear evidence that JMJD6 acts as a lysyl C-5 hydroxylase, interestingly giving the 5S- rather than the 5R- stereochemistry, and thus contrasting with the pro-collagen lysyl hydroxylases (80) (Fig. 2). The evidence for demethylation of N-methylated arginyl residues is much weaker, and there is no evidence for JMJD6 acting as a KDM.

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