lysozyme activity

[gocentral]

Hi,

Might the GO term - GO:0003796: lysozyme activity, be a gene product-specific term? Perhaps instead it should be called muramidase activity, or peptidoglycan N-acetyl muramoylhydrolase activity, with lysozyme activity as a synonym?

PMID: 16150577 has a section on Lysozymes.

cheers, Emily

Reported by: edimmer

Original Ticket: "geneontology/ontology-requests/2852":https://sourceforge.net/p/geneontology/ontology-requests/2852

[gocentral]

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The official name of EC 3.2.1.17 is lysozyme, with the alternative name muramidase. Perhaps "muramidase activity" should be added as a synonym to GO:0003796.

There are enzymes with lysozyme activity found in a broad range of organisms, so the term is completely appropriate for the GO.

-- Alex

Original comment by: addiehl

[gocentral]

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From the paper that Emily cited:

"Reportedly, the bacterial killing mechanism of lysozyme consists in the lytic and non-lytic mechanisms. The lytic mechanism includes enzymic peptidoglycan hydrolysis (muramidase activity) where lysozyme provokes cell lysis by hydrolyzing the peptidoglycan layers of bacteria, and induction of autolysins that are capable of causing bacterial autolysis. The non-lytic mechanism is principally based on the properties of lysozyme to cause membrane perturbation of its targets through the binding of a certain domain of lysozyme with the bacterial surface. Moreover, through its cationic and hydrophobic properties, lysozyme inhibits its targets via non-lytic mechanism. In addition, lysozyme denatured by heat or reduced by dithiothreitol, and recombinant lysozyme devoid of enzymic activity have been demonstrated to exhibit strong bactericidal activities independent of catalytic functions."

So lysozyme has two bacteriocidal methods, the first being the catalytic activity represented by the EC number, and the second being noncatalytic. It would probably be a good idea to rename the enzyme activity to something more structured so that there isn't any confusion about which of these two activities is being annotated.

Original comment by: girlwithglasses

[gocentral]

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I don't have access to the full-text or PDF version of PMID:16150577 through our library so I can't read the paper for myself. Please send it to me if possible. I am concerned that you are extrapolating from the human enzyme to all possible "lysozyme" enzymes the property of having two activities, when it could well be simply that the human or mammalian enzyme with lysozyme activity also possesses a second activity. I would also remind you that the EC commission probably represents far better knowledge and judgment on this issue than any of the three of us do. I'm also reluctant to base a term name change involving a better known enzyme activity on a single review. And remember, the definition of the GO term makes clear what reaction is involved.

Thus, I disagree entirely with renaming the term and will send this on to Harold for more comment. He's out today so you will have to wait a day for a reply.

-- Alex

Original comment by: addiehl

[gocentral]

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Hi Alex,

No problem, I think that Midori has already sent you a pdf of the paper. However if you are looking for this second, non-catalytic lysozyme acitivity within different species, there is information in: PMID: 11591365 and 12495010 using hen egg white lysozyme

cheers, Emily

Original comment by: edimmer

[gocentral]

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Emily,

Thanks for the paper references and the paper (Midori). Nevertheless if you look at

http://www.brenda.uni-koeln.de/php/ result_flat.php4ecno=3.2.1.17&organism=

you can see enzymes from a wide range of species, including bacteria and bacteriophage that are listed as having the EC lysozyme activity. I don't have time to research them all, but again, I prefer to defer to the EC people on this issue.

Lots of synonyms are available there too.

-- Alex

Original comment by: addiehl

[gocentral]

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Alex,

I think that you might be missing the point here. The point that I think Emily is making is that there are two bacteriocidal activities associated with lysozyme, one of which is the catalytic activity represented by EC:3.2.1.17, and the other of which was in the extract from the paper which I pasted in below. Emily's concern is that people may be annotating the latter noncatalytic activity to GO:0003796, which represents the catalytic reaction. Changing the term name to something more explicit - e.g. peptidoglycan N-acetyl muramoylhydrolase - would prevent annotators from using GO:0003796 to annotate the activity of anything described as 'lysozyme' and force them to consider whether the activity they were annotating was the catalytic reaction or the noncatalytic bacteriocidal activity.

For this reason, I think a term name change would be advisable.

Original comment by: girlwithglasses

[gocentral]

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It's worth noting that GO diverges from EC in a number of other cases, notably the proteases and cytoskeletal motors; often the reason is that the EC entry refers to a gene product or includes more process or component information than GO deems tolerable in the function ontology. EC classification is intended to be based on reaction mechanism, and in most cases it is, but in some places there are entries that are distinguished based on localization or other gene product attributes. In other words, EC (tho excellent) is imperfect, and GO is not constrained to follow EC where the latter is inconsistent with GO criteria.

m

Original comment by: mah11

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It is perhaps true that some annotators simply match keywords (from abstracts, no less) to GO terms, without bothering to attempt to understand the underlying science in the slightest degree, and thus might match a non-lysozyme activity of an enzyme referred to as lysozyme to GO:0003796 (which clearly did not occur here), but even if we change the name, we need to keep lysozyme activity as a synonym, which may continue to mislead annotators.

Thus, I don't think we're really solving any problem here, and I think we should simply leave the term name as it is. I will however, defer to Harold on this, since he is an actual biochemist.

I'm also awaiting a term proposal for the other activity of the vertebrate lysozymes in question.

-- Alex

Original comment by: addiehl

[gocentral]

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Hi,

I'm not too worried about curators getting confused. My point simply was that as the protein lysozyme has different bactericidal mechanisms, the term lysozyme activity becomes a description of a gene product rather than its muramidase catalytic activity.

The protein also seems to act (from studies with the chicken protein) by inserting into bacteria membranes and distorting lipid-lipid interactions (J. Afric. Food Chem, 1996, 44, 1416- 1423). The closest term reflecting this that I could find would be the process term: GO:0001901, cytolysis of cells of another, non- host, organism. I would consider requesting a child of this, such as 'membrane disruption in cells of another, non-host, organism'

cheers, Emily

Original comment by: edimmer

[gocentral]

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From the paper, it looks like the lytic mechanism would be annotated to lysozyme activity ; GO:0003796, plus new process terms under 'interaction between organisms' "induction of autolysin activity in other organism" and "cell wall peptidoglycan catabolism in other organism" (the wordings are a bit nasty, but hopefully the concepts are clear). The nonlytic mechanism would need new function terms for "bacterial cell surface binding" (could add Gram +ve / Gram -ve children), and then a new process along the lines of "membrane disruption in other organism"? Or maybe "cytolysis, by membrane disruption, in other organism"?

Any other term suggestions / name suggestions?

Original comment by: girlwithglasses

[gocentral]

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I just got in and saw this; let me take a look and get back in a few hours. Thanks; Basically, I think the term can stay; one could make "lysozyme activity" a synonym if one is concerned with someone referering to the wrong activity for an organism whose lysyzme has more than one distinct activity. I need to look at the paper; coffeeeeeee

Original comment by: hdrabkin

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I think changing the name to anything other than lysozyme will not help. If it were a synonym, and you pulled it up via searching for it, and the actual term name were Muramidase, I'm not sure that someone would still pick to annotate a lysozyme unless they knew that the reaction being described was the muramidase, and go no further But.... preuming they are looking at antibacterial activty . yes, peptides of lysozyme (at least hen lysozyme) appear to have anti-bacterial activity; is this a consequence of (like binding to the same target as the activity enzyme; ie, part of the active site), or something totally different? Do ALL lysozymes have this activity? If not, then perhaps we do need to distinquish when something called a lysozyme has the activity or not. Thus, all lysozymes are muramidases, but all lysozymes do not have non-enzymatic antivity.

Original comment by: hdrabkin

[gocentral]

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> If it were a synonym, and you pulled it up > via searching for it, and the actual term name were > Muramidase, I'm not sure that someone would still pick to > annotate a lysozyme unless they knew that the reaction being > described was the muramidase, and go no further

The paper would probably say something about peptidoglycan hydrolysis, though - you'd think annotators would see 'peptidoglycan' in the term definition and realize that was the enzymatic activity.

> But.... presuming they are looking at antibacterial activty [...] > Do ALL lysozymes have this activity? If not, then perhaps we > do need to distinquish when something called a lysozyme has > the activity or not.

Surely this doesn't matter? The GO term 'lysozyme activity' refers to the reaction that hydrolyses peptidoglycans; we'll be adding separate terms to describe the other processes that the particular lysozyme protein that Emily's paper refers to. These might have 'lysozyme' as a related synonym, but this will just be as a search aid.

I'll add those other terms and a bunch of synonyms for 'lysozyme activity' from the EC page - I think those are probably relatively uncontroversial...?

Original comment by: girlwithglasses

[gocentral]

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Hi,

This would work fine for me.

thanks, Emily

Original comment by: edimmer

[gocentral]

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OK, terms added:

GO:0051635 bacterial cell surface binding GO:0051636 Gram-negative bacterial cell surface binding GO:0051637 Gram-positive bacterial cell surface binding

GO:0051671 activation of autolysin activity in other organism GO:0051672 cell wall peptidoglycan catabolism in other organism GO:0051673 membrane disruption in other organism

If those terms are OK with everyone, I'll close this item.

Original comment by: girlwithglasses

[gocentral]

• status: open --> closed

Original comment by: girlwithglasses

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Closing...

Original comment by: girlwithglasses

[gocentral]

• milestone: --> TermGenie
• assigned_to: nobody --> girlwithglasses
• status: closed --> closed-accepted

Original comment by: girlwithglasses