Talk:Serpin

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Good article Serpin has been listed as one of the Natural sciences good articles under the good article criteria. If you can improve it further, please do. If it no longer meets these criteria, you can delist it, or ask for a reassessment.
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[edit] response to ideas, current state of play

All structural figures now added - on reflection I actually think that a TBG image would be better under a TBG page. Table reasonably well referenced Catalytic mechanism figure adapted and added as suggested. I have asked a colleague for an attractive cell biology figure to go at the top of the page More references added through out and some cleanup and wikifying performed (thanks to Arcadian and Kjaergaard) Have some ideas for additional sections - serpin folding, comment on exception to Anfinsens etc, illustrate phylogeny of superfamily, section on fly serpins and worm serpins.

Jcwhizz 09:39, 12 March 2007 (UTC)


[edit] Suggested additions to make before request general review

Polymer picture - combine with delta picture (in progress) Add "disease caused by deficiency" to human serpin list Add figure illustrating key serpin regions that are often mutated in human disease (Breach, shutter). Perhaps put in figure with conserved residues highlighted (or is this too specialised?) Expand polymer section and make more general linkages with protein misfolding Illustrate non-inhibitory section with picture of TBG, ligand and binding site highlighted. General cleanup, add a few more references, PMIDs where possible. Any other suggstions? Jcwhizz 00:59, 11 March 2007 (UTC)

In my opinion, the broad content in the serpin page is now scientificaly accurate, up-to-date, reasonably concise and appropriately structured (I have to admit to some bias, however, having written some of it!). I feel that the only major omission is a picture of a model of a serpin polymer (which I am making). I think there is still quite a bit of stylistic correction and cleanup to do. Major references in the field have been added, however, secondary references should probably be added too? I think the time is right for some more general feedback from the MCB comunity, however, I'm unsure how to start the review process. Jcwhizz 09:42, 11 March 2007 (UTC)

Right now the article is very good on the structural stuff, but contains very little about other aspects about serpins. This bias is probably related to the interests of the contributors. We need a beautiful picture to place in the top of the page to catch the interest of the readers. I think we need to show the catalytic cycle of serine proteases as well, showing explicitly where it is interupted. And I think the table should have the protein names as the first column, rather than the genes, since that are the names they are primarily known by... Kjaergaard 10:17, 11 March 2007 (UTC)

Agree with you on the structural bias (have to confess thats my area) and the catalytic cycle. However, there is a huge effort in the serpin community to stop using the "old" serpin names (which and to use the proper nomenclature SERPINA1 etc as the protein name - I will edit the Gene name to read Protein name (which is actually correct). I'll have a think about a beautiful (non structural) picture.

210.49.179.196 11:02, 11 March 2007 (UTC)

What do you think about a really attractively stained picture of a blood clot (appropriate given the large number of serpins involved in clotting / bleeding etc) or alternatively a white blood cell (rich in serpins) - not sure where to source these though as I don't have them myself. I have to confess I thought first about a nice picture of a serpin crystal - though on reflection I realised that possibly may be too structural...:) ?

Jcwhizz 11:29, 11 March 2007 (UTC)

And I'm pretty sure that PAI-1 doesn't inhibit plasmin directly. I don't know if you have a reference claiming this... Kjaergaard 10:20, 11 March 2007 (UTC)

Will check this out

210.49.179.196 11:02, 11 March 2007 (UTC)

Yup - my mistake - fixed

Jcwhizz 11:29, 11 March 2007 (UTC)

[edit] previous discussion

Serpin page coming together - some major and minor things to do. Major: 1) Add more figures (polymer). 2) More extensive referencing 3) Brief two liners about the function of each human serpin - for more in depth analysis should link to relevant pages 4) Section on serpin-enzyme complex uptake by LRP-related protein receptor. 5) Section on worm serpins

Minor Add PMID ids to references that do not have them Work out how to assign a unique number to a reference (i.e. so it is not repeated in the bibliography

Jcwhizz 05:26, 7 March 2007 (UTC)

What is the basis for saying that serpins are enzymes? As I understand it they are "suicide substrates". What reaction are they supposed to catalyze? Josh Cherry 23:15, 14 Jun 2004 (UTC)

In the strict sense of the word you're completely right. Perhaps we should revise nomenclature on this. By the way, how would you categorise these articles? JFW | T@lk 09:45, 15 Jun 2004 (UTC)


[edit] A topical serpin involved in malaria resistance - in mosquitoes!

The Monday, 24 October 2005 BBC News headline,

Malaria gene 'defends mosquitoes'

http://news.bbc.co.uk/1/hi/health/4370960.stm

...turns out to refer to this paper:

An immune-responsive serpin, SRPN6, mediates mosquito defense against malaria parasites

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16260729

The conclusion states that Anopheles stephensi SRPN6 is either directly or indirectly involved in the parasite-killing process, whereas Anopheles gambiae SRPN6 apparently acts further downstream on parasite clearance by promoting lysis.

(Mosquitoes with SRPN6 expression knocked out were ultra-susceptible to Plasmodium infection; steps are being taken to produce mosquitoes with a constitutively-active SPRN6 gene, to see what effect that has - immune mosquitoes in the wild would equal reduced Plasmodium transmission rates, until either the parasite or the insect evolved round it...)

Anyway, I just thought this might be germane to this article, but as this is the first time I've done anything on wikipedia, methought it better merely to mention it here so people can see what they think.

Cheers, Tommy B.

It might be more relevant to the Malaria article.... Kjaergaard 18:20, 15 April 2007 (UTC)

Thanks - have pasted it into the Talk:Malaria page, so people there can see what they thank. --Tommy B.

[edit] Lead suggestions

The lead has three functions. Firstly, the initial sentence should define the topic clearly and precisely without using too many technical terms. Secondly, the lead should introduce the topic and indicate why it is important. Thirdly, the lead should provide a brief summary of the main points in the article. The lead does an OK job of point one, but is still a bit short for points two and three. Aim for about three paragraphs? Tim Vickers 17:53, 28 July 2007 (UTC)

Hi Tim - good point - have expanded as suggested. Cheers James Jcwhizz 01:43, 29 July 2007 (UTC)

[edit] good article review

This is how the article, compares against the six good article criteria:

1. Well written?:
  • "and inflammation respectively" needs comma before "respectively"

Done Jcwhizz 00:13, 4 August 2007 (UTC)

  • Sometimes a bit verbose -
"The interest in these molecules was initially sparked as a result of their" could be put more succinctly "Initially, research focused on their.."
"While the majority of serpins function to control key extracellular and intracellular proteolytic cascades,..." could be better as "While most serpins control proteolytic cascades,..."
"As a result of their involvement in controlling medically important processes such as coagulation and inflammation, there is considerable interest in serpin function and serpin deficiency." could be better as "As serpins control processes such as coagulation and inflammation, these proteins are the target of medical research."
"The study of serpinopathies is useful for understanding the generalities of protein misfolding, a process that underlies other important human diseases such as Alzheimer’s and prion disease." could be better as "Undertanding serpinopathies provides insights on protein misfolding in general, a process common to many human diseases, such as Alzheimer’s and CJD."
"it is postulated that serpins inhibit both classses" could be better as "serpins may inhibit both classes"
"Analysis of Caenorhabditis elegans serpins revealed that all nine serpin genes lacked signal sequences and these are therefore are proposed to be intracellluar" could be better as "As all nine serpins in Caenorhabditis elegans lack signal sequences, they are probably intracellluar"
"The functional target(s) of intracellular inhibitory serpins have been more challenging to elucidate than their extracellular counterparts." could be better as "In contrast, the targets of intracellular inhibitory serpins have been more difficult to identify."
  • Over-use of the word "can" makes prose appear indecisive, "antitrypsin deficiency can cause emphysema", if this phenotype has high penetrance, just say "antitrypsin deficiency causes emphysema"
  • As a general rule, try to avoid the passive, past tense. It can make even these fascinating proteins appear very dull!
eg - *"in order to inhibit" is better as "when they inhibit" or "as they bind proteases, these proteins undergo a dramatic..." active, present tense makes most things read clearer and better.
  • You never need to say "have been shown to do X" or "studies have shown that X" or "recent research has demonstrated that X" all these phrases do not make your meaning any clearer but only add superfluous and distracting words. Just say "they do X" or "X is"
  • "Serpins also possess an exposed region termed the reactive centre (or site) loop (RCL) that (for inhibitory molecules)" - Too many parentheses (by far)!
  • "concomittently" - we're writing for the general public, "at the same time" or "simultaneously" are more widely-understood words.
  • "PAI-1 is released in the native conformation, however, rapidly undergoes conformational change" - I don't think this says what you intended.

Have gone through, made all the changes requested above, and also edited to make the article more succinct. Jcwhizz 00:13, 4 August 2007 (UTC)

2. Factually accurate?:
  • I've not come across "Archae" before, isn't Archaea the more usual term?

Sorry - spello. Jcwhizz 00:13, 4 August 2007 (UTC)

  • "These enzymes are defined by the presence of a serine residue in their catalytic site." Many, if not most enzymes contain at least one serine in their active site (which is where the link goes). It is the nucleophilic serine in the enzymatic reaction mechanism that defines this class.

Added the term nucleophilic to make this distinction for both serine and cysteine. Jcwhizz 00:13, 4 August 2007 (UTC)

  • "the lack of precise synteny between human serpins and the serpins of model organisms such as the mouse complicates functional characterisation." I don't understand this, if sequence similarity is high enough gene order is irrelevant, if order is conserved but sequence diverges,you can't assume shared functions. Surely sequence is more important than synteny?

Have replaced with functional orthology. Basically the problem is that the murine repotoire of serpins is vastly expanded with respect to human serpins. So for example, where there is one human gene for SCCA-1, there are 3-4 in the mouse. Thus it is difficult to know which one to knock out to gain an understanding of the role of the human protein. Jcwhizz 00:13, 4 August 2007 (UTC)

  • "cytotoxic granule protease granzyme B" is this an example of inappropriate intracellular activation of proteases? The way it follows this statement makes me suspect this, but the example doesn't explain enough for me to be sure.

Yes, in certain cases, for example in Tcell killing, there may be some "leakage" of Granzymes during granzyme delivery which are most likely mopped up by serpins such as PI-9. Have changed text to clarify this. Jcwhizz 00:13, 4 August 2007 (UTC)

  • I don't think allosteric modulators are often referred to as "cofactors", as this term is usually reserved for compounds required for an enzymatic activity. You could just say "binding of activators and inhibitors"

In this instance I think it is appropriate to - within the serpin field the term co-factor is generally accepted and used to describe molecules that modulate serpin inhibitory activity. See for example, Frank Church's recent review (Rau et al., J Thromb Haemost. 2007 Jul;5 Suppl 1:102-15) - but there many other papers on this topic. Jcwhizz 00:13, 4 August 2007 (UTC)

3. Broad in coverage?:
  • Yes.
4. Neutral point of view?:
  • A bit pro-serpin! :) but OK

Yes, I have to confess I have an interest :) Jcwhizz 00:13, 4 August 2007 (UTC)

5. Article stability?
  • Not a concern.
6. Images?:
  • The images are great, but the captions are a bit on the long side. Perhaps some of the text discussing the images, rather than just giving the components and colouring might be moved to the text?

Yes, good point - have shortened all legends, and moved the text of figure 4 (function of heparin) into the text. I have left the odd sentence to really emphasize key points. Jcwhizz 00:13, 4 August 2007 (UTC)


I've put this nomination on hold while the minor text changes are made. If you feel that this review is in error, feel free to take it to a GA review. Thank you to all of the editors who worked hard to bring it to this status. Tim Vickers 21:41, 31 July 2007 (UTC)

Thanks once again for a great and detailed review. Are you happy with the changes? Cheers James Jcwhizz 00:13, 4 August 2007 (UTC)

Very happy, congratulations it is a Good Article! Tim Vickers 14:13, 4 August 2007 (UTC)

Thanks Tim - excellent!! - I'll have a read on what is required for nomination for FA. Cheers James Jcwhizz 22:11, 4 August 2007 (UTC)

As a pointer for FA, the main areas to improve are the lack of a simple organisation, with structure and function interspersed, as well as the prose, which is still written for a specialist audience. I've always imagined FA science articles as aiming for Scientific American/New Scientist level of approachability. Perhaps the closest FA to this topic is the one on DNA, that might give some useful comparisons? Good luck and good writing! Tim Vickers 23:09, 4 August 2007 (UTC)

[edit] Problem with Figure 3

Figure 3, "Catalytic mechanism of serine proteases" - The reaction mechanism has some problems. The nitrogen in the carboxamide kinda disappears in the last couple steps and seems to maybe be replaced with an oxygen... —Preceding unsigned comment added by 65.67.67.220 (talk) 22:10, 8 November 2007 (UTC)

The cleaved product leaves the active site then water comes in to complete hydrolysis of the acyl enzyme intermediate. Not sure what problem you are refering to - looks like a pretty standard depiction of the reaction mechanism to me.

Jcwhizz 23:04, 9 November 2007 (UTC)

I made a modified version of the figure, is this any clearer? Tim Vickers 23:51, 9 November 2007 (UTC)

Hi - thats great!! Jcwhizz 08:37, 13 November 2007 (UTC)