Talk:Serpin

message: 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)
thread_title: response to ideas, current state of play

message: 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)
thread_title: Suggested additions to make before request general review

message: 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)
replies: text: 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)
thread_title: previous discussion

message: 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)
thread_title: A topical serpin involved in malaria resistance - in mosquitoes!

message: 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)
thread_title: Lead suggestions

message: 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)
replies: text: I made a modified version of the figure, is this any clearer? Tim Vickers 23:51, 9 November 2007 (UTC)
thread_title:  Problem with Figure 3 

message: Article is large and slow to format. It has over 170 references. Should we split it ?
Would it be sensible to split out Table 1 (which alone has over 70 references) ? Rod57 (talk) 09:12, 20 April 2011 (UTC)
thread_title:  Split to reduce size 

message: In response to a previous question by Jcwhizz of how to move this article to FA. Here are my suggestions (some of which I shall try to implement myself over the coming weeks).
===Content===
*The first section should probably be Activity and be about what they do i.e. inhibit proteases
::
*Historical information scattered through the article and lead should be gathered into a single section
:: I've moved the current historical info into a single section. Will need some more key dates in there (e.g. First discovered serpin? First structure?) 
*Lead should only summarise info from elsewhere in the article (and ideally proportionately to the size of each section)
:: I've removed unique information down to various sections of the article and tried to include a sentence or two on each main section
*The lead image should be the simplest to understand. From my limited knowledge, the PZI/PZ complex isn't the most common situation
:: I've made a new image for the lead that I hope includes the key points of a serpin 
*Several structure sections should be subsections under a general Structure section
::
*Similarly, the pathology sections should be grouped under one heading
::
*I'll actually semi-disagree with Tim Vickers here are suggest that the captions should describe the key point that the reader should understand from it (from the 2007 GA review)
**E.g it's not immediately obvious what the significance of the current Fig.12 is just from its caption
**I think it should still be possible to keep these succinct if a general audience is kept in mind
:: Tried to write short captions that highlight the specific point that the image is trying to convey.
*The Types and Disease sections could both be shortened by 20-40% to retain balance with the rest of the article
:: Types section neatened and shortened by default collapse of megatable
:: I've rearranged the Disease section so that the simpler-to-understand mechanisms of disease are given first
*There were 5 paragraphs and an image on the A-sheet model of polymerisation before it was then stated that it's thought to not be physiologically relevant.
:: I've removed it for now since it seems heavily over-weighted for a model that is no longer thought to be relevant. I think t that's reasonable given that this is not a historical review of overturned theories, but an encyclopedic summary of what is though to be the correct. I've saved the text below in case I'm missing something obvious though!
In the absence of definitive structural data, it was, therefore, postulated that serpins polymerise via a mechanism known as A-sheet polymerisation. In normal function the RCL inserts into the A β-sheet to form a fourth strand. In the A-sheet polymerisation model, it was suggested that the RCL of one serpin molecule spontaneously inserted into the A-sheet of another, to form a long-chain polymer (figure 9). In effect, it was, thus, proposed that polymerization occurred as a consequence of the requirement of the serpin scaffold to accept an additional β-strand.
Serpins were one of the first families for which disease-causing mutations were directly analyzed in reference to the available crystal structures. In support of the A-sheet polymerisation model, it was noted that many serpin mutations that cause polymerisation localise to two distinct regions of the molecule termed the shutter and the breach. The shutter and the breach contain highly conserved residues, underlie the path of RCL insertion, and are proposed to be important for conformational change.
Two structures of cleaved serpin polymers have been solved; both of which reveal RCL / A-sheet sheet linkages similar to those predicted by the A sheet polymerisation mechanism. However, in direct contrast to the known properties of physiological serpin polymers, crystals of cleaved serpin A-sheet polymers readily dissociate into monomeric forms.
Events associated with serpin polymerisation occur during the folding of the molecule, and that mutations that cause serpinopathies interfere with the ability of the serpin to fold to the metastable native state. In normal serpin folding, the serpin rapidly moves through a key folding intermediate to attain the native state. It is the serpin folding intermediate that has the ability to polymerise, hence it is important that this folding species rapidly moves on to adopt native state. Mutations such as the Z-antitrypsin variant (Glu 342 to Lys) somehow prevent the final stage of seprin folding and cause the accumulation of the folding intermediate. As a result, population of the folding intermediate resulted in polymer formation. It was noted that once folded, the Z-antitrypsin variant closely resembles wild-type material in terms of thermal stability and inhibitory activity.
Together, these data have presented an important challenge to the A-sheet model for serpin polymerisation. On the one hand, the idea that serpin polymer formation essentially takes advantage of the serpin mechanism of conformational change is an attractive one. On the other, the biophyiscal data in particular suggest that it is a folding intermediate (rather than the native form) that polymerises, and it is clear that this intermediate must have different structural properties to the native, folded state.
It is thought that physiological serpin polymers do not form via the A-sheet mechanism, but instead form via more extensive domain swapping events.
===Style===
*The page still contains a lot of scientific review-isms
**e.g. "It should additionally be noted that..." / "Early studies on serpins revealed that..." (removal doesn't change the sentence)
** e.g. "Rawlings et al. showed that..." (The researcher is irrelevant in this sentence, and is amply covered by the reference)
:: Reworded most of the main review-style statements.
*References to specific figures aren't really part of the style (since the number and order can change over time) and ideally the images stand alone anyway
:: I've gone through all of the cations to try to capture the key point being illustrated by the figure, whilst still retaining colour and PDB information.
*I agree that the classification mega-table should stay, but we could use a collapsed table to ease readability of the rest of the page (like in the catalytic triad article)
:: and also a few formatting changes to it
*The word serpin doesn't need to appear in the section headings
::
*Terms like 'recently' make the page harder to keep up to date. Dates can be used, or the recentness can be omitted all together
:: Important dates could maybe be included in the History section
*PDB codes should be auto-formatted by a template (more robust and easier to edit)
:: Have used  template in figure legends and  in the table
*PDB codes not in figure legends should probably be footnotes for the main text, since they're basically references
:: although there was actually only one occurrence in the end which later turned out to be redundant.
*Images should ideally have white backgrounds and full-resolution version should be >1000px wide.
:: I've updated several of the key images early in the article.
===Optional===
*Since the unique mechanism of these proteins is so visually striking, an animation would be ideal. However, this entirely depends on availability of something that can be put under a creative commons copyright license
With these changes, I think it'd be reasonable to submit it for FA nomination and see what the reviewers identify. Although it looks like a lot, I don't think it'll take too much to fix up these bits and pieces. T.Shafee(Evo﹠Evo)talk 11:27, 1 November 2015 (UTC)
thread_title:  How to move this to FA 

message: *Since the unique mechanism of these proteins is so visually striking, an animation would be ideal. However, this entirely depends on availability of something that can be put under a creative commons copyright license
With these changes, I think it'd be reasonable to submit it for FA nomination and see what the reviewers identify. Although it looks like a lot, I don't think it'll take too much to fix up these bits and pieces. T.Shafee(Evo﹠Evo)talk 11:27, 1 November 2015 (UTC)
thread_title: Optional

message: I've managed to do most of the big changes that I identified above ( and  changes).
The main changes have been:
* Rearrangement of the main headings to better group information
* General language simplification
* First sentences of all sections should be layman-understandable (hopefully)
* Updates of images to better highlight key points
* Removal of figure numbers and more descriptive captions
I've also taken the liberty of updating some of the images. Hopefully they're clearer. T.Shafee(Evo﹠Evo)talk 05:53, 20 December 2015 (UTC)
thread_title: Summary of changes (Nov-Dec 2015)

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thread_title:  External links modified