Talk:Catalytic triad

LBHB

the existance of a low barrier hydrogen bond in serine proteases is controversial at best; and it has been directly ruled out by high-res x-ray for alpha-LP: (http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/2006/128/i28/abs/ja057721o.html). i propose we revert that portion to something more like the previous version. Xcomradex 05:03, 19 February 2007 (UTC)

2013 overhaul

For such a fundamental enzymology page, this article has been in need of attention for a while. I've tried to keep what I could from the previous version.

Changes made

• Removed entirely the previous sections:
  • Example - The introduction sentences were sadly incorrect and misleading.
  • Amino acid sequence, histidine 57 - which simply looked at similarities between three S01 serine proteases
  • Four atom characterize different ASP-HIS-SER enzyme families - very specific point based on a single paper. I had hoped to integrate some the information elsewhere, however the original paper was too poorly written.
• Added non-protease examples
• Attempted to represent the range of different triads whilst emphasising their similarities
• Introduced sections on convergent and divergent evolution
• Added images to help clarify

To be done

• My background is in proteases. Examples from non-proteases would help to balance this article
• I aim to add a few images to illustrate the convergence and divergence (Complete 31 October 2013)
• Make sure that other relevant enzymology pages link to this (Complete 21 November 2013)

Evolution and evolvability (talk) 15:41, 27 October 2013 (UTC)

Class A

The level of detail and information in this article compares well with other Class A articles. Hopefully it can make it up to Good Article status with a bit more work.

• A history section would be useful by someone who's been in the field long enough to have a good knowledge of the old literature.
• Examples from other enzymologists on the triads from non-proteases would help give a more general view of triads.
• Additionally, perhaps chemists may have some input as to why the use of a triad is so common an active site construction

Evolution and evolvability (talk) 11:41, 1 December 2013‎ (UTC)

A few comments

Ha, Evolution and evolvability, when I first got here I started to respond to your previous posts without realizing they were from 2013! Had been meaning to look at this article since you mentioned it at WT:MCB last week but got distracted by the outbreak of stupidity around here (which probably went unnoticed by anyone who doesn't hang around the Broad Street pump ANI).

• The beginning of the history section is confusing. The structure was solved in the 1930s? That can't be right. And the reference (#6 at the moment) goes to a paper about administering endothelin to rats. There must be some typos in here. I think you mean trypsin was purified and crystallized in the 30s (Kunitz?).

 Done Ha, originally I'd written 'crystallised', then evidently forgotten what I was doing and changed it to 'solved the structure'. No idea how the Norothrop & Kunitz ref went so wrong though.

• A minor nitpick, but I personally prefer to use "hydroxyl" rather than "alcohol" for the functional group; I think it creates less confusion.

 Done You're right, and the wikilink goes through to hydroxyl anyway. I just really dislike the matching 'sulfhydryl', but I suspect it won't matter mixing thiol and hydroxyl.

Ha, I do this all the time and hadn't really thought about the parallelism fail :) Opabinia regalis (talk) 06:02, 10 July 2015 (UTC)

• Most of the text in the acid subsection is about various circumstances in which there is no acid.

 Done I've added some more detail on why Glu and Asp are the most common residues for this, to balance out the 'exceptions to the rule' examples.

• "Possibly low-barrier hydrogen bond" - it would be interesting to see a bit more detail on this dispute (which I take it is not resolved)

 Started Every time I think I'm getting to grips with this, the controversy turns out to be deeper and more complicated! I'll try to write a couple of sentences of summary and maybe update the LBHB page.

Oh good, then I will just read your summary and consider myself up to speed because I have completely lost track of this issue ;) Better than a review article! Opabinia regalis (talk) 07:58, 27 July 2015 (UTC)

 Done Ok, I've put together 4 references for the history section since the consensus (largely driven by Arieh Warshel) seems to be pretty definitively against it since the new millenium. I may put a more detailed description in the LBHB article, since it's probably not useful here.

• Kind of a hard problem to solve, but the description of the mechanism in words under Ser-His-Asp is definitely going to be hard to follow without a mechanism drawing like what's currently in the comparison section below. But there's enough text in between that even on my ginormous monitor I can't look at them both at once without opening a new window.

 Started I'm fixing this in a couple of ways. Firstly, I've moved a lot of the mechanism details to a dedicated function/mechanism section. Secondly, I'll make a clearer mechanism diagram to go in that section.

• Maybe highlight in a different color the relevant functional group for each example in the figure?
• "The chirality is reversed" - some confused premed is going to write on his exam that lipases have D-amino acids in them.

 Done Fixed to 'orientation of the triad members'

• You give the MEROPS classifications for proteases as you name them, but anyone who's decided to consult wikipedia about biochemistry has no idea what they mean and they're kind of obtrusive in short paragraphs (eg the cys-his-asp section). Maybe put them in endnotes?

 Done Definitely sensible. I've gone through and replaced with {{efn}} notes. I've also made {{MEROPS}} to link them out (e.g. {{MEROPS|clan=PA|fam=S1}} → MEROPS: clan PA, family S1.

• "Nucleophilic enzymes..." - are enzymes whose mechanisms involve nucleophiles described as "nucleophilic"?

 Done I think you already fixed this, but you're right, no one really says a "nucleophilic enzyme".

• "Here I concentrate on..." - this isn't a review paper :) This whole section reads as a bit too technical.

 Done I've split up this section so that its integrated into the simpler information in the rest of the article. I think I was just keeping it together since that's the way I'd originally written it.

• There's some repetition in the convergent evolution section.

 Done Fixed!

• There's a lot of references to the oxyanion hole but neither article has a picture of one the way it's usually depicted in textbooks; eg. this or this one.

 Done I've added one of the images you suggested into the oxyanion hole article, and largely rewritten it (though it's still a stub). I found some nice references at least.

• For interesting non-proteases, sinapoyltransferases/plant SCPLs come to mind. I don't know of a case where the catalytic triad occurs in a non-protease that doesn't have obvious protease ancestry.

 No action I've read up a bit on these guys. Since they're not yet on wikipedia, and their reactions are not trivial to describe, I'll leave them for now. I've added in a few other interesting non-protease examples though.

Opabinia regalis (talk) 00:54, 2 July 2015 (UTC)

@Opabinia regalis: Thank you for your detailed read-through, it's really helpful to have someone else cast their eye over the article. I'll tick off your points above as I go through correcting the article. T.Shafee(Evo﹠Evo)^talk 12:02, 2 July 2015 (UTC)

You know, I just noticed you'd already nominated it for GA. I should've just done an official review given the insane backlog over there. Sorry. But all those checkboxes and cutesy graphics give me a headache. Opabinia regalis (talk) 21:36, 2 July 2015 (UTC)

References