SEA-PHAGES | Metalloprotease or metallopeptidase

Link to this post \| posted 24 Nov, 2020 17:10
hnance@ccga.edu	Has anyone determined they had evidence to call a function as metallopeptidase, rather than metalloprotease? I asked Debbie and she gave this very helpful response: First, does your protein have the sequence to be able to call it a metallo-(whatever)? That sequence is HELGH The answer: Yes! it does: MGVRVRTAVTPNGWWGAYDHRRRLITLRPGLGPIQLKCTLMHELGHAHYGHTGVTGKQEALANRWAAYRLINFEDVLALASVEQSSSGVAAALEVMPDVLETYLQLLTRAQLGALRTAALSRVA From my quick reading, a peptidase is a particular kind of protease, specifically cleaving peptide bonds at the N or C terminus of a protein. Because we don’t know where it cleaves (and this is the part that I don’t know enough), I would stick with metalloprotease (because it includes the peptidases). I would be inclined to keep it a broader term, but if you can provide evidence that it contains a specific activity, metallopeptidase is not off the table. We thought this may be a good question to ask the forum - any additional insight would be appreciated! Thanks!

Link to this post | posted 24 Nov, 2020 17:10

Has anyone determined they had evidence to call a function as metallopeptidase, rather than metalloprotease? I asked Debbie and she gave this very helpful response:

First, does your protein have the sequence to be able to call it a metallo-(whatever)? That sequence is HELGH

The answer: Yes! it does: MGVRVRTAVTPNGWWGAYDHRRRLITLRPGLGPIQLKCTLMHELGHAHYGHTGVTGKQEALANRWAAYRLINFEDVLALASVEQSSSGVAAALEVMPDVLETYLQLLTRAQLGALRTAALSRVA

From my quick reading, a peptidase is a particular kind of protease, specifically cleaving peptide bonds at the N or C terminus of a protein. Because we don’t know where it cleaves (and this is the part that I don’t know enough), I would stick with metalloprotease (because it includes the peptidases).

I would be inclined to keep it a broader term, but if you can provide evidence that it contains a specific activity, metallopeptidase is not off the table.

We thought this may be a good question to ask the forum - any additional insight would be appreciated! Thanks!

Link to this post \| posted 25 Nov, 2020 00:26
cdshaffer	These issues of specificity are always difficult to annotate. I agree with Debbie in that I tend to "do no harm"; that is, I would annotate using the more general "protease" unless there is good evidence for the more specific term. To answer the question of function at this level you would have to dig into the published literature on the matching crystals and see if they describe the active site in detail. If you are lucky you can find enough detail as to exactly which bonds are involved in the reaction and which side chains are critical in the active site. If you can get that, then you could see if your protein is likely to create that same active site using 3D modeling and visualization tools. This is well beyond what I ask students to do in general but we ask students to investigate one gene "in depth" and this would be a really good candidate gene for this kind of detailed investigation. The likelihood of success is low, and I tell my students that up front, as they have to be lucky enough that the information they are looking for is actually in the published literature. But as a teacher I am fine with students trying as it is really about the journey not the destination. Edited 25 Nov, 2020 00:29

Link to this post | posted 25 Nov, 2020 00:26

cdshaffer

These issues of specificity are always difficult to annotate. I agree with Debbie in that I tend to "do no harm"; that is, I would annotate using the more general "protease" unless there is good evidence for the more specific term.

To answer the question of function at this level you would have to dig into the published literature on the matching crystals and see if they describe the active site in detail. If you are lucky you can find enough detail as to exactly which bonds are involved in the reaction and which side chains are critical in the active site. If you can get that, then you could see if your protein is likely to create that same active site using 3D modeling and visualization tools. This is well beyond what I ask students to do in general but we ask students to investigate one gene "in depth" and this would be a really good candidate gene for this kind of detailed investigation. The likelihood of success is low, and I tell my students that up front, as they have to be lucky enough that the information they are looking for is actually in the published literature. But as a teacher I am fine with students trying as it is really about the journey not the destination.

Edited 25 Nov, 2020 00:29

Link to this post \| posted 25 Nov, 2020 00:51
hnance@ccga.edu	Thanks so much for your insight here! I appreciate the help - Holly

Link to this post \| posted 13 Apr, 2022 14:37
debbie	It was pointed out to me (Thanks Mitch!) that the motif needed to include "metallo" in your gene call of a metalloprotease is HEXXH. Sorry for the confusion.

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Metalloprotease or metallopeptidase