Wikipedia:Featured article review/Enzyme inhibitor/archive1

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The following is an archived discussion of a featured article review. Please do not modify it. Further comments should be made on the article's talk page or at Wikipedia talk:Featured article review. No further edits should be made to this page.

The article was kept by Nikkimaria via FACBot (talk) 2:32, 6 August 2022 (UTC) [1].

Enzyme inhibitor[edit]

Notified: TimVickers, Molecular Biology, Pharmacology, talk page notification 2020-12-13

This was noticed near the end of 2020, there is a bunch of problems with the articles. Unsourced sentences, the images are laid out messily, the writing needs a overhaul. There are a lot of issues with this article that I don't think will be fixed. GamerPro64 23:02, 25 March 2022 (UTC)[reply]

I have reordered a few of the sections, corrected a few inaccuracies, improved the image layout, and have added a few citations. I will add more as I find time. Any additional problems? Boghog (talk) 14:23, 26 March 2022 (UTC)[reply]
Definitely looks improved from the previous version. Gonna need another take from someone more seasoned with medical articles at least. GamerPro64 04:44, 29 March 2022 (UTC)[reply]
@Boghog: I am not a medical expert (maybe SandyGeorgia can suggest a couple of editors to take a look at this?) but I'll give some general thoughts below as a non-expert reviewer. I noticed that there's lots of paragraphs that either do not have citations or do not have one at the end. When I write historical bios, I typically require a citation at the end of the every paragraph, minimum, to verify the preceding information. I'm not sure how it is with MED articles, as there are formulas involved, so instead I will post some of these paragraphs without citations below:
  • There's a couple of paragraphs that do not have citations that concern me. One place is the "Types" section (under "Reversible inhibitors"): uncompetitive inhibition has a citation at the end of its paragraph but the other do not. What is verifying the information in the other three paragraphs, and should there be a citation at the end of them?
  • Under "Quantitative description" there are paragraphs between formulas that are not cited. I am confused about which sources are verifying this information. Is there a way that citations can be added to these paragraphs?
  • The first paragraph in "Measuring" does not have citations. Is citation 33 verifying this information?
  • The first paragraph in "Applications" does not have citations. What is verifying this information?
  • The second paragraph in "Antibiotics" does not have citations. What is verifying this information?
  • The first paragraph in "Pesticides" does not have citations. What is verifying this information?
I hope this gives a good start in things to consider. Please ping me if you have any questions. Z1720 (talk) 03:30, 3 April 2022 (UTC)[reply]
Thanks Z1720 for your comments. I am gradually adding more citations to the sections that you mention. Under the Quantitative description section, the second half of the section was added after the the article was promoted to FA in this edit, is fairly technical, and the only support I could find was in a predatory source. Prehaps it would be best to delete this material altogether. Boghog (talk) 10:24, 3 April 2022 (UTC)[reply]
I do not have the subject-area expertise to comment on what should and should not be in the article, so I will defer to other's judgement. Z1720 (talk) 15:30, 3 April 2022 (UTC)[reply]
There is too much text uncited that should be cited, inappropriate use of bolding, and while I am not easily frightened by biomedical topics, I can get no sense from the lead of ... anything. The lead needs to be brought down a level, into plainer English, less jargon. SandyGeorgia (Talk) 00:28, 4 April 2022 (UTC)[reply]
Thanks SandyGeorgia for your comments. Most material is now supported by citations, inappropriate bolding removed, and the lead has undergone signficant copyedits, so hopefully it is now more accesssible. Boghog (talk) 12:13, 9 April 2022 (UTC)[reply]

I haven't read through yet.

  • Is interfers British spelling?
  • "For example, in the Lineweaver–Burk plots at the right, ... " nothing at the right ... so a complete read-through is needed.

SandyGeorgia (Talk) 13:43, 9 April 2022 (UTC)[reply]

I updated the lead to make it more accessible for laypeople and corrected some minor misspellings and whatnot. Surprisingly, „interfers“ is not (yet) accepted British spelling. But I daresay it will be someday, as a posher variant of gofers — looks better on a résumé, no? ;)
I also clarified the text regarding the Lineweaver-Burk plots, to make it easier to recognize which diagrams are meant and how they illustrate the type of inhibition (competitive vs. non-competitive).
I've also done a quick scan through the article to find mistakes, but not yet a thorough read-through. Willow (talk) 10:38, 16 April 2022 (UTC)[reply]

I am going to be traveling for my son's wedding, and won't be able to follow progress on this nom for several weeks, but on a quick final glance I see:

  • Paragraphing in the lead makes no sense and it is still not lay-reader friendly.
  • WP:CITATION OVERKILL ... maximum reaction rate catalyzed by the enzyme) and Km (the concentration of substrate resulting in half maximal enzyme activity) as the concentration of the enzyme's substrate is varried.[2][4][5][6][7]: 132–167 
  • Still some text that is uncited that needs citation.
  • Still some MOS:BOLD wonkiness.
  • A complete read-through is needed.

GamerPro64 I won't be available to help bring this one over the line. Perhaps you can enlist Graham Beards? SandyGeorgia (Talk) 13:52, 21 April 2022 (UTC)[reply]

Thanks SandyGeorgia for your constructive comments. Concerning the lead, for context, it should brefily put in context what an enzyme is and why it is important, but perhaps it could be trimmed back a bit to focus more closely on inhibitors, and that might make it a bit easier to digest. Concerning the single bolded term that is not in the lead sentence, covalent reversible inhibitors is a redirect, and hence is an allowed exception to MOS:BOLD. I will work on adding more citations to other parts of the article and remove citation overkill. Congrats to your son and enjoy your trip! Boghog (talk) 16:15, 21 April 2022 (UTC)[reply]
Thanks! I can follow from iPad, but can't do much to help. SandyGeorgia (Talk) 17:28, 21 April 2022 (UTC)[reply]
  • Could we get an update on status here? Nikkimaria (talk) 04:20, 7 May 2022 (UTC)[reply]
    I think all the concerns raised above have now largely been addressed. If there are any remaining issues, please let me know and I will try to fix them. Just one note in passing. Above it was suggested that we need a medical review. However, with the exception of the Enzyme_inhibitor#Drugs section, this article is more within the scope of WP:MCB than WP:MED. Boghog (talk) 06:54, 7 May 2022 (UTC)[reply]
    This section (for example, natural poisons and drugs) contains biomedical/health statements that I don't feel qualified to assess; the article needs a medical reviewer. SandyGeorgia (Talk) 21:10, 1 June 2022 (UTC)[reply]
    Reliable secondary sources should be sufficient to support statements about poisons. We are not going to run randomized double blinded clinical studies to confirm that exposure to nerve gas causes deaths in humans. That would obviously be unethical. Animals studies + ancidotal human evidence is more than sufficient. Statements such as 1/3 of currently approved drugs are enzyme inhibitors are uncontroversial and are backed up by reliable secondary sources already included in the article. Boghog (talk) 19:09, 5 June 2022 (UTC)[reply]
  • Acronyms are used before they are defined (eg, ATH, NADH); check throughout needed. SandyGeorgia (Talk) 20:53, 1 June 2022 (UTC)[reply]
    Hopefully I caught all the remainder in this series of edits. Boghog (talk) 10:19, 5 June 2022 (UTC)[reply]
  • User:Evad37/duplinks-alt reveals a number of duplicate links, but they are probably justifiable by the complexity of the topic; I have rejigged to avoid some Easter egg links, and that should be checked throughout. SandyGeorgia (Talk) 20:54, 1 June 2022 (UTC)[reply]
  • The lead image and caption are not explaining to the layreader what an enzyme inhibitor is, rather providing too much detail that isn't helpful to the lay reader, who will access the lead. SandyGeorgia (Talk) 20:56, 1 June 2022 (UTC)[reply]
    • @Evolution and evolvability:. Your figure is beautiful and a big improvement over the figure that it replaced, but is not as dead simple as it should for the lead of a featured article. I can simplify the caption, but I am not nearly the artist that you are. Something similar to this might get the point across more clearly. Can you make something similar? In addition, something like this figure would be great further down the article. Cheers. Boghog (talk) 18:44, 3 June 2022 (UTC)[reply]
      I agree - It probably makes sens to have a highly sinplified variant for the lead image. I'll get on it this week. T.Shafee(Evo&Evo)talk 10:04, 5 June 2022 (UTC)[reply]
    Thanks! I have put in place holder "pac-man" figures, but please feel free to replace. Cheers. Boghog (talk) 16:58, 5 June 2022 (UTC)[reply]
    I've added some updated figures throughout, aiming to use similar colour schemes to those used in enzyme. I've also edited the kinetic mechanisms to use the Ki' making system (rather than the old Kii nomenclature) as I think it's more common these days. A number of publications use the αKi nomenclature, but it's used inconsistently and more complex inhibitor suituations use a different nomenclature again (example) I've also tried to make the italicisation consistent, but please do check if I've missed any! T.Shafee(Evo&Evo)talk 07:56, 13 June 2022 (UTC)[reply]
    The new graphics are perfect! Both dead simple and visually pleasing. Also thanks for your other edits. Cheers. Boghog (talk) 10:36, 13 June 2022 (UTC)[reply]
    No worries! I might also try to make something for metabolic regulation within pathways (including end-product regulation) as I think it's easiest when visualised. T.Shafee(Evo&Evo)talk 12:46, 13 June 2022 (UTC)[reply]
  • I have removed external jumps from image captions and completed incomplete image captions: this citation needs to be completed. Unsure if that should be a cite web or a cite journal. SandyGeorgia (Talk) 21:06, 1 June 2022 (UTC)[reply]
    It is both a journal citation and a Protein Data Bank entry. Added both in this edit. Boghog (talk) 19:25, 3 June 2022 (UTC)[reply]
  • A short description of why each item is included in See also would be helpful. SandyGeorgia (Talk) 21:11, 1 June 2022 (UTC)[reply]
    Added in this edit. Boghog (talk) 19:25, 3 June 2022 (UTC)[reply]
  • Unique sub-headings: the heading "Examples" is used twice. SandyGeorgia (Talk) 19:31, 3 June 2022 (UTC)[reply]
    Not sure how to address this. The "Types" and "Examples" subheadings are used twice, but they are under different headings, "Reversible" and "Irreversible", so it is implied that the headings mean "Reversible types", "Irreversible examples", etc. We could spell out the implied meaning, but that would violate WP:HEAD (don't repeat heading titles in every subheading). Alternatively, a synomyn could be used, but I cannot think of any good synomyms to use in this context. Boghog (talk) 09:23, 5 June 2022 (UTC)[reply]
    I think it's reasonable to repeat subheadings under different headings in this context, and the shorter Types subheadings are definitely better than Types of reversible inhibitors etc. T.Shafee(Evo&Evo)talk 12:18, 13 June 2022 (UTC)[reply]
    It is a bit problematic though, as it messes with section linking processes. Enzyme inhibitor#Types will always go to the first use of the section heading. Hog Farm Talk 13:38, 20 June 2022 (UTC)[reply]
    I have addressed that issue; there are still remaining issues. MOS:SEEIMAGE. Throughout, the text refers to image placement with words such as "on the right", etc. Images display in different places on different browers; this needs to be redone. @Buidhe, Hog Farm, and Z1720: do you find the lead accessible to a layperson? SandyGeorgia (Talk) 15:10, 20 June 2022 (UTC)[reply]
    I'll give it a read-through over my lunch break. Hog Farm Talk 15:11, 20 June 2022 (UTC)[reply]
    I found it comprehensible. Hog Farm Talk 17:37, 20 June 2022 (UTC)[reply]
  • While complying with MOS:COLOR can often be difficult, and not a reason alone for opposing an image, it is awkward to have a lead image that breaches MOS:COLOR and that contains excess information. A simpler lead image is still needed. SandyGeorgia (Talk) 15:16, 20 June 2022 (UTC)[reply]
    The bottom row of the lead graphic (File:Enzyme inhibitors.svg) depicts allosteric inhibition and is not directly discussed in the lead. I have therefore replaced it with a new version (File:Enzyme inhibitors 2.svg) which removes the bottom row. I think the remaining information is very relevant to the lead and does not contain any excess information. The top row depicts what an enyzme does (first paragraph of lead), and the bottom row depicts how an inhibitor works (second paragraph of lead). The current colors do not pass the contrast standards for the color impaired. However the graphic does contain symbols for enzyme (E), substrate (S), product (P), and inhibitor (I). I have added these symbols to the caption. Boghog (talk) 10:13, 24 June 2022 (UTC)[reply]
  • A jargon check/wikilinking check is needed throughout; eg, isomerization, Acetylcholinesterase inhibitor doesn't seem to be linked. Pls check throughout. SandyGeorgia (Talk) 15:19, 20 June 2022 (UTC)[reply]
    I have added a number of wiki links for technical terms and provided explained what a dissociation constant is in this edit. Boghog (talk) 11:11, 25 June 2022 (UTC)[reply]
  • Review throughout for MOS:CURRENT issues; time context is needed for statements like "More recently, an alternative approach has been applied: rational drug design uses the three-dimensional protein structure of an enzyme's active site to predict which molecules" ... something like ... since the 1970s, in the 21st century, etc. Similary, missing as of dates, sample: "currently approved drugs are enzyme inhibitor". Similarly, but also indicating the article is still dated: "repeated until a sufficiently potent inhibitor is produced.[95] Computer-based methods of predicting the affinity of an inhibitor for an enzyme are also being developed, such as molecular docking" is cited to 2003: "also being developed" still ??? Updates needed. Another example of a MOS:CURRENT, missing as of date, is: "An estimated 29% of currently approved drugs are enzyme inhibitors[74] of which approximately 1/3 are kinase inhibitors."
  • Concerning MOS:CURRENT, in this edit, I specified when. Concerning molecular docking which was mentioned in the Discovery and design of inhibitors section, the entire section was out-of-date and read like an advertisement for virtual screening. While virtual screening is useful, it is only one many strategies that are used in modern drug disocovery. Therefore I have completely rewritten this section based on more recent secondary sources. Hopefully the section is now more balanced. It needs some additional copy edits and I am working on this. Boghog (talk) 11:20, 25 June 2022 (UTC)[reply]

This issues indicates that a top-to-bottom check for WP:WIAFA compliance and comprehensive rewrite has not yet been done. Shall we MOVE to FARC or is someone able to do a comprehensive check and update? SandyGeorgia (Talk) 15:28, 20 June 2022 (UTC)[reply]

Thanks again for your constructive criticisms. All issues that have been identified above have been fixed. The introduction section was not as accessibe as it should have been, but it has been extenstively rewritten and now it should be understandable to a wide audience. The Drugs section was also rewritten to bring it up-to-date and to broaden its scope. The Discovery and design of inhibitors section had some neutrality issues and also was not up-to-date. This section has been completly rewritten to adress these concerns. I have gone over the rest of the sections and in my opinion, they look like they are in good shape. Basic enzymology concepts that are presented in the Reversible and Irreversible inhibitor sections have not changed that much over the last 20 years. Furthermore I think these sections were well written and organized to begin with. Hence I don't think these sections require a comprehensive rewrite. The main problems with these two sections were lack of citations and jargon, but these has been fixed. Of course, if any additional issues are identified, I will work to correct them. Boghog (talk) 09:09, 26 June 2022 (UTC)[reply]
The article did a good job explaining what enzyme inhibitors do, but only in passing mentioned what they are. A new Structural classes section has now been added to provide a more complete description of what enzyme inhibitor are composed of (small molecules and proteins).Boghog (talk) 11:59, 12 July 2022 (UTC)[reply]
  • Wikipedia does not seem to have anything to link to for clarifying cleave. Wiktionary has it as "splitting", while regular dictionaries have it as "adhering to". Which is the case here? Can a parenthetical be inserted on first occurrence of the word cleave? SandyGeorgia (Talk) 14:01, 12 July 2022 (UTC)[reply]
    Yes, "splitting" is correct. Jo-Jo Eumerus (talk) 14:04, 12 July 2022 (UTC)[reply]
    Thanks, parenthetical added. SandyGeorgia (Talk) 14:06, 12 July 2022 (UTC)[reply]
  • Is repell BrEng? If so, can we add an inline comment so others won't change it? SandyGeorgia (Talk) 14:06, 12 July 2022 (UTC)[reply]
    That is a typo. It is spelled repel (wikt:repel) in both American and British English. Now fixed. Thanks for catching this. Boghog (talk) 09:24, 13 July 2022 (UTC)[reply]
    Struck, SandyGeorgia (Talk) 09:37, 13 July 2022 (UTC)[reply]
  • The lead says AIDS, the body says HIV. SandyGeorgia (Talk) 14:15, 12 July 2022 (UTC)[reply]
    Fixed, struck. SandyGeorgia (Talk) 09:34, 13 July 2022 (UTC)[reply]
  • Links to "sections above" won't work on Wikipedia mirrors, and need to be spelled out, as do things like "discussed above (where)? I have added inline queries. SandyGeorgia (Talk) 14:34, 12 July 2022 (UTC)[reply]
    See Wikipedia talk:Featured article review/Enzyme inhibitor/archive1, Samples of linking ... SandyGeorgia (Talk) 18:25, 13 July 2022 (UTC)[reply]
    Based on this suggestion, I have added internal wiki links between text that refer to imgages and the images themselves. Does this work? An alterative would be to include a figure number in each of the captions (figure 1, figure 2, etc.) and refer to the figure number. I cannot find any style guidline that would discourage this, but it does not seem to be widely practiced. Disadvantages of this aproach are maintenance and longer figure captions. Boghog (talk) 18:30, 13 July 2022 (UTC)[reply]
    See Wikipedia talk:Featured article review/Enzyme inhibitor/archive1 for alternate suggestion to use the title header on images, and refer to those. What is done now is a GREAT start, but doesn't work on Wikipedia mirrors. SandyGeorgia (Talk) 19:18, 13 July 2022 (UTC)[reply]
    Also, you can do a ctrl-f search on WHERE? to locate the other instances that need fixin'. SandyGeorgia (Talk) 19:25, 13 July 2022 (UTC)[reply]
    OK, thanks for the hint. I have removed all the links to images and replaced with reference to image headers. I have also searched for "see", "above", "below", and "right". Hopefully all references to images have been fixed. Boghog (talk) 20:27, 13 July 2022 (UTC)[reply]
    Much better ... I like it! But you still have to ctrl-f on WHERE? ... there are still several. SandyGeorgia (Talk) 20:39, 13 July 2022 (UTC)[reply]
    Missed your inline comments. Now working on it. Boghog (talk) 12:40, 14 July 2022 (UTC)[reply]
    Switched them so they will be easier to see [2] SandyGeorgia (Talk) 15:55, 14 July 2022 (UTC)[reply]
  • Which dimer should be linked? SandyGeorgia (Talk) 14:37, 12 July 2022 (UTC)[reply]
    Done, struck. SandyGeorgia (Talk) 21:35, 12 July 2022 (UTC)[reply]

Noting my queries above, @Z1720, GamerPro64, and Hog Farm: for a new look. Jo-Jo Eumerus are you satisfied ? SandyGeorgia (Talk) 14:51, 12 July 2022 (UTC)[reply]

Sorry, it's summer and I have wound down my Wikipedia reading so I haven't done any deep reading here. Jo-Jo Eumerus (talk) 15:11, 12 July 2022 (UTC)[reply]
It's on the list for me. Although I should note that I'm not going to be very scientific-literate (my wife was shocked to find out that I don't know how many chromosomes a human has). Hog Farm Talk 23:13, 12 July 2022 (UTC)[reply]
  • MOS:COLOUR on the DFP reaction diagram; can it be redone to use a schematic other than color? See, for example, the maps at Great Fire of London. It should not be difficult to do that without dependence on color. SandyGeorgia (Talk) 18:38, 13 July 2022 (UTC)[reply]
    Technically challenging, but this may be a solution. I am working on it. Boghog (talk) 12:40, 14 July 2022 (UTC)[reply]
    Great! I would not hold up a FAC or FAR over this, but we should try to fix it when it's doable. SandyGeorgia (Talk) 15:56, 14 July 2022 (UTC)[reply]
    The lead image has been modified to add a checkerboard pattern to the inhibitor binding site. The substrate and inhibitor can be described by their shapes (rectangle and rounded rectangle respectively). The figure caption has also been modified to supplement the color legend with pattern/shape descriptions. I experimented with adding pattern to the substrate and inhibitor, but the results were not very aesthetic. Hopefully the shape descriptions are adequate. Boghog (talk) 15:45, 16 July 2022 (UTC)[reply]

This loses me:

  • The binding of an inhibitor and its effect on the enzymatic activity are two distinctly different things, another problem the traditional equations fail to acknowledge. It is further assumed that noncompetitive inhibition results in 100% inhibition of the enzyme, and fails to consider the possibility of partial inhibition.
    "Two distinctly different"? --> ?? --> Another problem the traditional equations fail to acknowledge is that the binding of an inhibitor and its effect on the enzymatic activity are distinct.
    --> ?? The equations assume that noncompetitive inhibition results in 100% inhibition of the enzyme, and fail to account for partial inhibition.

SandyGeorgia (Talk) 05:14, 15 July 2022 (UTC)[reply]

  • I agree that this was ackwardly worded. The general idea is that binding ≠ inhibition. Binding of a molecule to an enzyme does not guarantee it will inhibit, and if it does inhibit, the inhibition may be less than 100%, even if the enzyme is completely occupied by the inhibitor. I have edited this paragraph and hopefully it is now clearer. Boghog (talk) 11:02, 16 July 2022 (UTC)[reply]

This will not work on Wikipedia mirrors (which don't have Wikilinks); the "above" has to be explicitly named in text:

  • Proteins can also be natural poisons or antinutrients, such as the trypsin inhibitors (discussed above) ... imagine the text without wikilinks, how does the reader know what is being referred to above?

SandyGeorgia (Talk) 05:17, 15 July 2022 (UTC)[reply]

Comments posted at Wikipedia talk:Featured article review/Enzyme inhibitor/archive1#HF. Hog Farm Talk 04:42, 19 July 2022 (UTC)[reply]

Close w/o FARC, my concerns have been addressed. Hog Farm Talk 13:20, 21 July 2022 (UTC)[reply]
Many anti-viral drugs are enzyme inhibitors. The article mentions this indirectly in the lead but it is not followed up in the body. I think the article needs a paragraph on this. Graham Beards (talk) 17:52, 21 July 2022 (UTC)[reply]
See, I thought that many drugs period are enzyme inhibitors... Jo-Jo Eumerus (talk) 21:08, 21 July 2022 (UTC)[reply]
I can write the section if you agree. Graham Beards (talk) 22:13, 21 July 2022 (UTC)[reply]
I agree. I made a start. Feel to expand and edit. Boghog (talk) 12:59, 22 July 2022 (UTC)[reply]
I don't think we need much more. We should stress that the enzymes inhibited are mainly virus-encoded and not host ones. Also this citation, Kausar S, Said Khan F, Ishaq Mujeeb Ur Rehman M, Akram M, Riaz M, Rasool G, Hamid Khan A, Saleem I, Shamim S, Malik A (2021). "A review: Mechanism of action of antiviral drugs". International Journal of Immunopathology and Pharmacology. 35: 20587384211002621. doi:10.1177/20587384211002621. PMC 7975490. PMID 33726557. is not the best. It is poorly written, has numerous grammatical errors and is difficult even for me to understand. (Please forgive my immodesty). This one is much better: Bamford, Dennis; Zuckerman, Mark A. (2021). Encyclopedia of virology (4th ed.). Amsterdam. pp. 11, 129. ISBN 978-0-12-814516-6. OCLC 1240584737.{{cite book}}: CS1 maint: location missing publisher (link) - Graham Beards (talk) 15:47, 22 July 2022 (UTC)[reply]
Thanks for the suggestion. The Encyclopedia of Virology comes in five volumes and I tracked down the chapter "Antiviral Classification" starting on page 129 to volume 5. I agree it is a much better source and as a bonus, that chapter is freely available, so I have updated the source. What volume/chapter does page 11 refer to? Boghog (talk) 16:45, 22 July 2022 (UTC)[reply]
I don't know where I got "11" from. Graham Beards (talk) 17:02, 22 July 2022 (UTC)[reply]
OK, the "Antiviral Classification" chapter is sufficient. Boghog (talk) 19:02, 22 July 2022 (UTC)[reply]

Sorry for the late reply but I'm perfectly fine with closing without an FARC. GamerPro64 06:05, 31 July 2022 (UTC)[reply]

The above discussion is preserved as an archive. Please do not modify it. No further edits should be made to this page.
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