NTR protein deamidation

[amandamackie]

NTR: protein deamidation

Def: the removal of amide groups from asparaginyl (Asn) and glutaminyl (Gln) residues in proteins

Is a GO:0006464 cellular protein modification process

Refs: PMID 11606750 and PMID 6304723

[pgaudet]

Hi @amandamackie Is this process mediated by a protein ? Looking quickly at the papers it seems like they measure deamidation of target proteins, not which proteins mediate the deamidation.

('targets' of processes should not be annotated to the process).

Thanks, Pascale

[amandamackie]

Hi Pascale,

Yes, CheB in E. coli mediates deamidation of chemoreceptor proteins. Actually I just saw the term GO:0018199 which is peptidyl glutamine modification so glutamine deamidation could be a child of that. I'll try and dig up a better reference

Amanda

[pgaudet]

Great thanks - that wasn't obvious from the papers you sent (apologies if I didn't look closely enough though!)

[pgaudet]

Looking (quickly again) at https://en.wikipedia.org/wiki/Protein-glutamate_methylesterase, based on the fact that E. coli CheB (P07330) is annotated to EC 3.1.1.61 (http://www.sbcs.qmul.ac.uk/iubmb/enzyme/EC3/1/1/61.html), it looks like the enzyme catalyzes a demethylation, not a deamidation?

[amandamackie]

Yes, it does both - it deamidates glutamine residues (EC3.5.1.44) and it demethylates methylglutamates. It's all part of the adaption response in bacterial chemotaxis. Here's a review paper PMID 9442881 in Table 1 you can see that CheB is described as a methylesterase/amidase

[hdrabkin]

Interesting; PMID:25367007 states "Deamidation of asparagines and glutamines occurs spontaneously in proteins and results in protein degradation. Deamidation of asparaginyl residues in proteins produces a mixture of asparaginyl, n-aspartyl, and isoaspartyl residues, which has been linked to the pathology of some neurodegenerative disease"; PMID:11606750 does not really mention an enzymatic activity, but appears to measure spontaneous deamidation of purified proteins (?). However, PMID: 6304723 does show evidence that Che-B appears to mediate the deamination of a specific residue

Question: Has this ever been shown with a purified protein product in vitro (ie, Che-B in a test-tube)?

BUT, Even if non-enzymatic, the rates could be enhanced/regulated by other proteins (like Che-B).

[deustp01]

Question: Has this ever been shown with a purified protein product in vitro (ie, Che-B in a test-tube)?

Answer: Sort of. See PMID:10919788 / PMCID:PMC92152 for a description of experiments in which an enzyme partially purified from the soil bacterium Chryseobacterium proteolyticum sp. nov. deaminated casein in vitro in studies said to distinguish deamidase activity from transaminase activity (which can mimic deamidase activity under the right assay conditions).

[amandamackie]

In reviews on bacterial chemotaxis, CheB is described as an MCP-specific methylesterase and deamidase. The sites of methyl esterification in the E. coli methyl-accepting chemotaxis receptor proteins (ie the MCPs Tar, Tsr, Trg and Tap) are well characterized – some of these sites are glutamates which can be directly methylated/demethylated, others are glutamine residues which are first deamidated to glutamic acid and then methylated/demethylated.

PMID 25834953 (Parkinson 2015) is a recent review which states:
“CheB, an MCP-specific methylesterase and deamidase, preferentially interacts with ON-state receptors and shifts them toward the OFF state, either by hydrolyzing methylated glutamates or by irreversibly deamidating glutaminyl residues to glutamic acid at some adaptation sites in newly synthesized receptors”.

The body of work cited as evidence for CheB catalysed demethylation and deamidation will typically include references such as: PMID 6758950 (Kehry 82), 6300110 (Kehry 83), 2254280 (Park90), 3032955 (Nowlin87), 2033064 (Rice 91).

[amandamackie]

Based on the above, the term that I require is peptidyl or protein glutamine deamidation; my apologies for not being more specific in the first instance Def: removal of amide groups from glutaminyl (Gln) residues in proteins

[hdrabkin]

maybe 'peptidyl/protein glutamine deamidation' would do the trick.

[pgaudet]

Isn't this inconsistent with other similar terms? Ie they are all named 'peptidyl...', aren't they?

Le mar. 10 juil. 2018 à 3:46 PM, Harold Drabkin notifications@github.com a écrit :

maybe 'peptidyl/protein glutamine deamidation' would do the trick.

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[hdrabkin]

We would then really need to say peptidyl-WHAT deamination. So is, therefore, should be peptide deamidation, like peptide modification, or peptide amidation.

[hdrabkin]

No; under peptide modifcation, there is a single term peptide amidation, which if one looks is NOT an amino acid side chain modification

Actually we may need two process terms, each specifying the target amino acid:

one a child of peptidyl-glutamine modification the other a child of peptidyl-asparaginyl modification

[pgaudet]

@kaxelsen emailed me this:

As I see it, CheB is most probably a deamidase in addition to a demethylase, but there might not be clear-cut biochemical evidence to back the claim. I will report this to HAMAP and let them judge.

So without more evidence of the existence of this reaction, should we add it ?

[ValWood]

Hi @kaxelsen any feedback on this?

[kaxelsen]

In a way yes. EC 3.5.1.44 has been added to all the CheB proteins and in the entry from Halobacterium salinarum, i saw When I pmid:18514223, in which one finding is: "CheB is required for Htr deamidations, at least at a specific glutamine–glutamate pair in Htr2 and a specific aspartate–glutamine pair in Htr4." It should be noted that this is not done with purified proteins but by MS/MS anaylsis of peptides from a size fraction of the entire proteome.

[ValWood]

what is the action here now that we no longer add modifications to the BP ontology?

[pgaudet]

Hi @amandamackie As @ValWood points out, we are not creating these types of biological processes anymore - ie processes that correspond exactly to a MF. If you'd like another term, such as a signaling pathway, we can create this, but otherwise in this case we would conclude that the bp that the enzyme is involved in is unknown.

Thanks, Pascale