User talk:Kitaylor/sandbox

Peer review by Nhat Do
In case the authors want to expand their writing on the mechanism, here are my suggestions: Thanks. Nhat Do. Nhattrongdo (talk) 01:18, 4 March 2017 (UTC)
 * The group provided a well-organized article on the mechanism of tryptophan 7-halogenase. They used 7 references for their article. The article is well-written and I personally think the tone is encyclopedic.
 * For spelling or grammar, everything is good. I just have a concern on some words like “7 position” or “2 position”. I think the authors want to mention “C7 position” and “C2 position”.
 * 1. Be more extensive in the regiochemistry part, especially provide a Pymol picture which can illustrate better the structure of the tunnel and a comparison between position C2 and C7 of tryptophan’s indole ring in the active site of the enzyme. Also, giving more detail about tryptophan 5-halogenases is suggested as they mentioned it at the end but did not clarify what tryptophan 5-halogenases can benefit from having carbon 5 in the end of the tunnel.
 * 2. Give a short description on the mechanism proposed by Flecks et al as it does not include the formation of the chloramine species which is a more common concept. Did Flecks et al propose any intermediate species?
 * 3. Also are there any recent updates on the halogenation step as three references used in this part (mostly reference 7) are published in 2005 and 2007?
 * 4. The first and third paragraphs of “Halogenation mechanism” are not linked to any reference, so it is not clear if they are written based on the reference 4, 7 and 8.
 * 5. Provide the caption for the images. The authors have great images though.
 * 6. The authors mentioned in the last paragraph that the enzyme has been studied using X-ray crystallography, so in my opinion, it can be better if the authors also briefly mention the methods employed to arrive at the conclusions on the mechanism mentioned right before that.

Introduction
It catalyzes formation of carbon-halogen bonds at the nucleophilic carbon 7 position found on the indole ring of the amino acid tryptophan. The two tryptophan-7-halogenases discussed in this article are RebH and PrnA.
 * It catalyzes THE formation of carbon-halogen BOND at the nucleophilic C-7 position OF the indole ring OF tryptophan.
 * I do not think it is an appropriate expression in an encyclopedia article.

Background
Tryptophan-7-halogenases were first identified in 1998, during studies of the pyrrolnitrin biosynthetic gene cluster of Pseudomonas fluorescens. The gene, PrnA, was found to halogenate tryptophan at the C7 position.  Specificity of the flavin reductase is not required, as different flavin reductases all supported halogenase activity. Discovery of tryptophan 7 halogenases opened up a new class of halogenases.
 * You need a reference for the original discovery.
 * I think the nomenclatures for gene and corresponding enzyme are different. Should it be PrnA?
 * I would use "support" instead of "supported".
 * First, name of the enzyme is "tryptophan-7-halogenases".
 * This sentence actually repeats the same idea for twice.

Mechanism
Tryptophan 7-halogenases are FADH2-dependent
 * Tryptophan-7-halogenases are FADH2-dependent

For sustained activity in an in vitro setting
 * Do you mean "For sustained activity in vivo an in vitro setting"?
 * Also, it should be in vitro.

Halogenation of tryptophan’s indole ring at carbon 7 is a result of electrophilic attack on Cl+ species.
 * I would say "say halogenation of C-7 position of the indole ring in tryptophan".
 * Cl+ species.


 * I think the sub-title is better with "Regioselectivity".
 * Again, tryptophan-7-halogenases

tryptophan 7-halogenases catalyze their reaction with high efficiency and specificity.
 * I would say "The tryptophan-7-halogenases catalyzed reaction showcase high efficiency and specificity".
 * efficiency is not necessary here since you are talking about selectivity.

Overall view

 * 1) The language of this article is not what we expect to see in the encyclopedia.
 * 2) Although the article does show the mechanism, the poor structure of the mechanism section indicates the lack of logic.

I think the main takeaways from these reviews are as follows: 1. review the regioselectivity part and improve/flesh out our explanations there 2. review Flecks' suggested mechanism (perhaps a smaller subheading? not sure? 3. double check references for halogenation mechanism 4. captions!!!!! 5. briefly discuss methodology in corresponding sections! 6. review language and compare with wikipedia's guides... (not sure if I think this is a major problem?) 7. check grammar Some of the second review suggests that we aren't going in depth enough--worth discussing how we can preserve readability while including more depth. My interaction with articles like these came most often in high school in Science Olympiad, so I'd like a high-schooler to be able to read this article easily. Our citations should better serve scientists looking to read in more depth. — Preceding unsigned comment added by Kitaylor (talk • contribs) 00:26, 9 March 2017 (UTC)

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Jared notes============= 1. the intro paragraph is not consistent with other articles on specific enzymes. this should be about RebH. you can note that there are other trp-7-halogenases. 2. it is ok to lead with trp-7-hal in the background, but i am very confused about the final sentence of the review. this is not referring to trp-7-hal, and is very confusing since the sentences before and after do. i would structure as: historically, hal involved haloperox (not sure about perhydrolases btw). then trp-7-hal identified in 98. then make your general points about these enzymes 3. cycle: show Cl- attacking O, rather than H of -OH group; also need H+ in this step 4. mech: reformat so that all reagents are left of the arrow; it is not known if the lysine is protonated or not during halogenation write as: NH2 -> Cl-NH(H+) 5. are you sure that RebF (rather than other reductases) is natively expressed in multiple organisms? 6. use super/subscripts were relevant (e.g. Cl+) 7. " long lived species (half-life > 28 hours)" --citation! 8. "To get around this, the enzyme promote fast reaction with lysine 79, and only once the chlorinating intermediate is formed does the substrate, tryptophan, bind to the enzyme." definitely need a citation here also. 9. RebH really doesn't have high catalytic "efficiency" in terms of rate. not clear what you mean, but i would just focus on selectivity — Preceding unsigned comment added by Jared Lewis (talk • contribs) 19:17, 13 March 2017 (UTC)