NTR: children of monophenol monooxygenase activity etc

[gocentral]

We have had a bit of a struggle finding the correct terms to annotate the prophenoloxidases described in this paper: PMID:22120533 == Li et al., 2012, Dev. Comp. Immunol. 36(4): 648--656 Properties of Drosophila melanogaster prophenoloxidases expressed in Escherichia coli. I think a few extra synonyms and possibly two new terms could help.

The authors in this paper say they are measuring prophenoloxidase activity. They test three enzymes (PPO1, PPO2, PPO3) with three different substrates and show that:

All 3 can oxidise L-DOPA and dopamine But only PPO1 can also oxidise L-tyrosine

All reactions are copper dependent.

Suggestions/questions:

1. Add Prophenoloxidase as a synonym to monophenol monooxygenase activity ; GO:0004503

Prophenoloxidase doesn’t match any GO terms but Prophenol oxidase is a related synonym for monophenol monooxygenase activity ; GO:0004503.

2. While monophenol monooxygenase activity is probably the term we need, we are confused by the definition since it implies that BOTH L-tyrosine and L-DOPA are in the reaction together whereas our paper assays each substrate separately.

def: "Catalysis of the reaction: L-tyrosine + L-DOPA + O2 = L-DOPA + DOPAquinone + H2O." [EC:1.14.18.1]

Is that just a mis-interpretation of the def on our part - does it mean L-tyrosine and L-DOPA are alternative substrates rather than both being required for the reaction? The enzyme name is very non-specific suggesting it may well have multiple substrates. Could this be clarified in the def please? The IntEnz view of this EC number gives only a single reaction RHEA:18120 L-tyrosine + O2 <=> L-dopaquinone + H2O - not sure what to conclude from that.

3. Ideally, we would like to capture the fact that only PPO1 works well with both L-tyrosine and L-DOPA. Could we make two child terms to represent the two specific substrates and make the current def more generic? I’m guessing that you may prefer this to go in Col16 but we don’t have it and I think even if we clarifed that the substrates are alternative we’d have to make sure it didn’t imply that it necessarily did both reactions.

We notice that there is already the term tyrosine N-monooxygenase activity ; GO:0050370 but we assume this is a different reaction?

4. Also add prophenoloxidase as a related synonym to catechol oxidase ; GO:0004097

There is the following comment in on EC:1.14.18.1 in KEGG:

“A group of copper proteins that also catalyse the reaction of EC 1.10.3.1 catechol oxidase, if only 1,2-benzenediols are available as substrate.”

Catechol oxidase (def: Catalysis of the reaction: 2 catechol + O2 = 2 1,2-benzoquinone + 2 H2O) does seem to represent the reaction with the third substrate dopamine (according to chEBI dopamine is a catechol). So I think it would help to have prophenoloxidase as a related synonym here too.

Could we add dopamine oxidase activity as a narrow synonym to catechol oxidase ; GO:0004097. We already have the broad synonym dopa oxidase - but shouldn’t this be a narrow synonym?

Reported by: stweedie

Original Ticket: geneontology/ontology-requests/9386

[gocentral]

• assigned_to: nobody --> rfoulger

Original comment by: rebeccafoulger

[gocentral]

Mark suggested these websites to look for products of L-DOPA and dopamine oxidation:

http://www.brenda-enzymes.org/php/ligand\_flatfile.php4?brenda\_ligand\_id=10197

http://www.brenda-enzymes.org/php/ligand\_flatfile.php4?brenda\_ligand\_id=3273

Original comment by: rebeccafoulger

[gocentral]

We need to split 'monophenol monooxygenase activity ; GO:0004503' into it's different reactions. For Susan's annotations at least:

1. Monooxidation of L-tyrosine
2. Monooxidation of L-DOPA (precursor to dopamine)
3. Monooxidation of dopamine

The confusion with EC:1.10.3.1 (catechol oxidase) comes because EC uses these as grouping terms, and says that monophenol monooxygenases catalyse monooxygenation of monophenols to dipenols (EC:1.14.18.1) and oxidation of catechols (diphenols) to quinones (EC:1.10.3.1). So they are separate activities.

Since we'd prefer to make oxidoreductase function terms for reactions 1-3 (rather than x oxidation process terms), Susan will email the authors to see if they can tell us the reaction products when L-DOPA and dopamine are used as substrates.

Original comment by: rebeccafoulger

[gocentral]

Couple more things, while I remember:

The reason why L-DOPA appears on both sides of the reaction in EC:1.14.18.1 is because it's acting as a cofactor: PMID: 4965136. 3,4Dihydroxy-L-iphenylalanine as the Tyrosinase Cofactor

Also, when creating terms for the different substrates: L-tyrosine = a monophenol L-DOPA = a diphenol (so comes under catechol oxidase activity ; GO:0004097)

Original comment by: rebeccafoulger

[gocentral]

Updated the definition and synonyms of monophenol monooxygenase activity ; GO:0004503 Added a comment in about L-DOPA can act as a cofactor in mammals. Also added comment that the term (unlike the EC!) exclusively refers to monooxygenation of monophenols, and to to annotate to the catechol oxidase term for diphenols (catechols).

Created new terms under 'catechol oxidase activity ; GO:0004097' for: L-DOPA monooxygenase activity ; GO:0036263 dopamine monooxygenase activity ; GO:0036264 I've put '?' in the definitions for the products: when these become clear, we can update the terms.

Hope that allows you to annotate away.

Cheers, Becky

Original comment by: rebeccafoulger

[gocentral]

• status: open --> closed-fixed

Original comment by: rebeccafoulger