Talk:Catalytic triad/GA1

GA Review
The edit link for this section can be used to add comments to the review.''

Reviewer: Stigmatella aurantiaca (talk · contribs) 22:40, 10 August 2015 (UTC)

Beginning review. I will be adding my comments over the next few days. Stigmatella aurantiaca (talk) 22:40, 10 August 2015 (UTC)

Passes copyvio test Earwig's Copyvio Detector Stigmatella aurantiaca (talk) 22:50, 10 August 2015 (UTC)

History
 * "A serine in each of trypsin and chymotrypsin was identified as one the catalytic nucleophile (by diisopropyl fluorophosphate modification) in the 1950s." (Unclear phrase: "as one the catalytic nucleophile")
 * "The structure of chymotrypsin was solved in the 1960s" (Using X-ray crystallography, of course.)
 * "The MEROPS classification system in the 1990s and 2000s started to class proteases into structurally related enzyme superfamilies" ("Started to class"? They don't any longer? Why the past tense?)
 * ✅ T.Shafee(Evo&#65120;Evo)talk 10:53, 17 August 2015 (UTC)

Function
 * "Enzymes that contain an catalytic triad use it for one of two reaction types: either to split a substrate (hydrolases) or transfer one portion of a substrate over to a second substrate (transferases)." (Defective sentence parallel structure. Should be "or to transfer")
 * "They occur as an inter-dependent set of residues" (Unclear pronoun antecedent. Does the word "They" refer back to "Enzymes", "catalytic triad", "substrate" or what? Replace with "Catalytic triads".)
 * "Catalysis occurs because the triad residues act together" (Verbose. Suggest "The triad residues act together")
 * ✅ T.Shafee(Evo&#65120;Evo)talk 10:57, 17 August 2015 (UTC)

Mechanism Stigmatella aurantiaca (talk) 11:18, 11 August 2015 (UTC)
 * "In order to generate a nucleophilic enough residue for catalysis, the functional groups of the other triad members are used to increase its reactivity." (Reword in non-teleological terms. Avoid using words suggesting "purpose" or "design". For example, suggest "The reactivity of this nucleophilic residue is increased by the functional groups of the other triad members" or some other such wording.)
 * "If this substrate is water then the result is hydrolysis, if it is an organic molecule then the result is transfer of that molecule" (Run-on sentence. Use a semicolon or period rather than a comma.)
 * ✅ Well spotted. I'd not noticed how teleological the writing sounded. T.Shafee(Evo&#65120;Evo)talk 11:03, 17 August 2015 (UTC)

Noticed by the peer review tool Stigmatella aurantiaca (talk) 11:41, 11 August 2015 (UTC)
 * Please make the spelling of English words consistent with either American or British spelling, depending upon the subject of the article. Examples include: honor (A) (British: honour), ization (A) (British: isation), isation (B) (American: ization), catalyse (B) (American: catalyze), hydrolyse (B) (American: hydrolyze), sulphur (B) (American: sulfur).
 * Add a "British English" template to the Talk page if British English is your intention. There are some online spell checkers that you can use. It won't necessarily be possible to stamp out 100% of the mixed usages (eg. in quotes, wikilinks, references), but you should try.
 * ✅ I've added the template. T.Shafee(Evo&#65120;Evo)talk 12:47, 17 August 2015 (UTC)

Nucleophile
 * "The lone pair of electrons present on the oxygen or sulphur attack the electropositive carbonyl carbon." (Number agreement. "The lone pair...attacks" not "attack".)
 * "Embedding the nucleophile in a triad is necessary to increase its reactivity for efficient catalysis." (Avoid teleological language. "Embedding the nucleophile in a triad increases its reactivity for efficient catalysis.")
 * "Alternatively, threonine proteases use the secondary hydroxyl of threonine, however such proteases have to use their N-terminal amide as the base, rather than a separate amino acid, due to steric hindrance of the extra methyl group."
 * Telelogical language
 * Steric hindrance of which extra methyl group? I presume you mean that of threonine.

Stigmatella aurantiaca (talk) 22:20, 11 August 2015 (UTC)
 * "Serine is therefore more dependent on other residues to reduce its pKa for concerted deprotonation with catalysis by optimal orientation of the acid-base triad members" (Unclear run-on sentence. Do you mean that the constraints on orientation of the other triad members are more stringent than with other amino acids?)
 * "Sterically, the sulphur of cysteine also has longer bonds and a bulkier Van der Waals radius to fit in the active site" (Do you mean that it is less able to fit in the active site?)
 * "and a mutated nucleophile can be trapped in unproductive orientations" (I presume that you mean that experimental replacement of cysteine with other nucleophiles results in trapping of the mutated nucleophile in unproductive orientations. This is not clear.)
 * ✅ T.Shafee(Evo&#65120;Evo)talk 10:21, 18 August 2015 (UTC)

Base Stigmatella aurantiaca (talk) 22:32, 11 August 2015 (UTC)
 * "Since no natural amino acids are strongly nucleophilic, the base in a catalytic triad polarises and deprotonates the nucleophile to increase its reactivity." (Teleological language. Try something like "No natural amino acids are strongly nucleophilic. The base in a catalytic triad polarises and deprotonates the nucleophile, increasing its reactivity.")
 * "It is most commonly histidine since its pKa allows for effective base catalysis as well as both hydrogen bonding to the acid residue and deprotonating the nucleophile residue." (Unclear pronoun antecedent. What is "It"? Sentence parallel structure is a bit messed up. Try something like "The base is most commonly histidine since its pKa allows for effective base catalysis, hydrogen bonding to the acid residue, and deprotonation of the nucleophile residue.")
 * "In order to avoid steric clashes, threonine proteases use their N-terminal amide as the base, to increase the reactivity of the catalytic threonine residue." (Teleological language)
 * ✅ T.Shafee(Evo&#65120;Evo)talk 10:32, 18 August 2015 (UTC)

Acid Stigmatella aurantiaca (talk) 22:41, 11 August 2015 (UTC)
 * "Cytomegalovirus proteases uses a pair of histidines" (Number agreement. Proteases use, not uses.)
 * ✅ T.Shafee(Evo&#65120;Evo)talk 11:33, 19 August 2015 (UTC)

Examples of triads Stigmatella aurantiaca (talk) 11:00, 12 August 2015 (UTC)
 * "This allows the histidine to act as a powerful general base and activate the serine nucleophile." (Parallel structure. "and to activate".
 * "It also has an oxanion hole consisting of several backbone amides for stabilising charge build-up on intermediates." (Teleological language. Try "which stabilises")
 * "Removing the acid histidine only results in a 10-fold activity loss" ("results in only a 10-fold activity loss" rather than "only results in a 10-fold activity loss", which would imply that the activity loss is the only effect. Unless you really mean that that is the only outcome, of course.)
 * "This triad has been interpreted as a possible way of generating a less active enzyme to control cleavage rate." (OK, I'll allow this. It isn't your teleological interpretation, but the interpretation of Ekici et al.)
 * "The middle serine then forms two strong hydrogen bonds to he nucleophilic serine" ("to he" -> "to the" or "with the")
 * "The triad is further unusual in that the lysine and cis-serine both act as the base in activating the catalytic serine but the same lysine also performs the role of the acid member as well as making key structural contacts." (Use a comma before the "but" since it separates two independent clauses. The rules on commas can be a bit complicated.)
 * ✅ T.Shafee(Evo&#65120;Evo)talk 11:33, 19 August 2015 (UTC)

Divergent evolution
 * "Additionally, an alternative transferase mechanism has been evolved by amidophosphoribosyltransferases in which the catalytic cysteine of one domain hydrolyses a glutamine substrate to release free ammonia, which diffuses though an internal tunnel in the enzyme to a second active site, where the ammonia is transferred to a second substrate." (Excessively long sentence)
 * "Despite chemical differences between the possible triad nucleophiles, some protease superfamilies have evolved from one nucleophile to another through divergent evolution." (Initial clause seems superfluous. Try "Some protease superfamilies have evolved from one nucleophile to another through divergent evolution" or similar wording.)
 * ✅ Split the first mega-sentence into three, and have also clarified significance 'Despite chemical differences' in separate sentence. T.Shafee(Evo&#65120;Evo)talk 11:46, 19 August 2015 (UTC)

Convergent evolution Stigmatella aurantiaca (talk) 03:54, 14 August 2015 (UTC)
 * "leading evolution to independently converge on equivalent solutions repeatedly." (Most modern English usage guides have dropped the objection to the split infinitive, but this is an especially bad example. Try "leading evolution repeatedly and independently to converge on equivalent solutions.")
 * "Similarly, the same has occurred with cysteine proteases such as viral C3 protease and papain[c] superfamilies." (Try "Similar convergent evolution has occurred...")
 * "Consequently, most threonine proteases use an N-terminal threonine in order to avoid such steric clashes" (Teleological phrasing)
 * "Two evolutionarily independent enzyme superfamilies with different protein folds are known to use the N-terminal residue as a nucleophile; Superfamily PB (proteasomes using the Ntn fold) and Superfamily PE (acetyltransferases using the DOM fold)" (Use full colon instead of semicolon)
 * ✅ T.Shafee(Evo&#65120;Evo)talk 12:00, 19 August 2015 (UTC)

Response
Thank you for a thorough read of the article. I've gone through an addressed the points you raised (almost always using your suggested wording). In particular, thank you for pointing out how teleological some of my writing has been. I'm going to take greater care in future to catch myself. T.Shafee(Evo&#65120;Evo)talk 12:03, 19 August 2015 (UTC)
 * You're welcome! I really enjoyed this article. It's been twenty years since I last taught a biochemistry class, and it is always amazing to me to see the progress in this science! Stigmatella aurantiaca (talk) 16:10, 19 August 2015 (UTC)