User talk:Gbzwg/sandbox
Please note: Spelling and grammar errors are in bold.
Too many subheaders under "Function and Mechanism"
Perhaps move history closer to the top? Since it discusses background related to some of the topics discussed in the function and mechanism section.
Intro:
- Need to get rid of "An Error has occurred retrieving Wikidata item for infobox" at beginning of article.
- Lysozymes are enzymes (EC 3.2.1.17) that damage bacterial cell walls by catalyzing the hydrolysis of peptidoglycan, the major component of gram-positive bacterial cell walls.
- May not need this sentence: "Peptidoglycan is formed by alternating N-acetylmuramic acid(NAM) and N-acetyl-D-glucosamine (NAG) monomers through β-(1,4) linkages. "
- Lysozymes catalyze hydrolysis of β-(1,4) linkages in bacteria by compromising the integrity of the cell wall.
- Lysozymes have also been shown to catalyze the hydrolysis of chitodextrins, although at slower rates than chitinases.
What are chitinases? Confusing to compare the rate of catalysis to something not previously mentioned. Also, you should add a source for this statement.
Function:
If possible add another sentence or two to function.
- It attacks peptidoglycans, its natural substrate, between N-acetylmuramic acid(NAM) and the fourth carbon atom of N-acetylglucosamine(NAG).
You do not need to repeat "peptidoglyans (found in the cell walls of bacteria, especially Gram-positive bacteria)" because this info is already in the intro.
- "From x-ray crystallography data, Phillips proposed the lysozyme's active site binds to a hexasaccharide." Need a source!
Phillips Mechanism:
- The Phillips Mechanism proposes that the enzyme's catalytic power comes from both steric strain on the bound substrate and electrostatic stabilization of the oxo-carbonium intermediate.
- Thus, distortion lowers the energy barrier of the reaction by causing the substrate to adopt a strained conformation similar to that of the transition state.
- The oxo-carbonium intermediate was also proposed to be electrostatically stabilized by Arieh Warshel in 1978. It is suggested that residues in the active site, such as aspartate and glutamate are able to stabilize this intermediate. The electrostatic stabilization argument is based on comparison to bulk water, the reorientation of water dipoles can cancel out the stablizing energy of charge interaction.
"and especially lower the when to ions are close to each other." What were you trying to say here?
"There were some contadictory results to indicate the exact RDS." Reword to sound more encyclopedic, such as "The RDS is still unknown, although extensive research has been done in this area."
Koshland Mechanism:
- In an early debate in 1969, Dahlquist proposed a covalent mechanism for lysozyme based on isotope effect
Put figure title in box instead of typed into the picture.
- More recently, quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations have been completed using the crystal of HEWL to predict the existence of a covalent intermediate.
- Evidence from ESI-MS and X-ray structures indicate the existence of a covalent intermediate, but primarily rely on using a less active mutant or non-native substrate.
Inhibition:
- Imidazole derivatives can form charge-transfer complex with some residues (in- or outside active center) to achieve competitive inhibition of lysozyme.
Enzyme Conformation Changes:
- Lysozyme exhibits two conformations: an open active state and a closed inactive state.
Need a source for the second half of the paragraph or move source to end of paragraph.
Role in disease:
Did you try to find a source for the sentence with "citation needed"? And find a better source for the one with "not in citation given"?
TessaColameta (talk) 21:34, 1 March 2017 (UTC)
Article Draft Review
Introduction Section:
Lysozymes catalyze hydrolysis of the β-(1,4) lysing the bacteria by compromising the integrity of its cell wall
- There should be a word right after β-(1,4), probably bond or link.
Lysozymes also have been shown to be able to catalyze hydrolysis of chitodextrins, although at slower rates than chitinases.
- Add a link to Chitinases article, and add some comment about chitodextrins being the natural substrate of chitinases. A reference for this statement is also needed.
From x-ray crystallography data, Phillips proposed the lysozyme's active site binds to a hexasaccharide.
- Does this mean that the native substrate is a hexasaccharide, or that only six saccharide units from the polysaccharide are involved in binding to the active site?
Function and Mechanism Section:
- Probably there is no need for a Function heading, since that sub-section contains only two sentences. Could this information be combined with some other part of the section?
- The Active Site Section needs references.
- The images in the Active Site Section could be resized to avoid empty spaces at the sides of the structure.
- The image that compares both proposed mechanism could be made more compact to reduce empty space.
The Phillips Mechanism proposed that the enzyme's catalytic power came from both steric strain on the bound substrate and electrostatic stabilization of the oxo-carbonium intermediate.
- This paragraph is only one sentence long.
The lysozyme distorts the fourth sugar in the hexasaccharide into a half-chair conformation.
This oxo-carbonium intermediate was also proposed to be electrostatically stabilize by Arieh Warshel in 1978
- Should replace stabilize for stabilized, or maybe stable.
In Warshel's model, the enzyme acts as a super-sovlent (solvent), which fixes the orientation of the ion pair and provides super-solvation, and especially lower the (word missing) when to (two) ions are close to each other.
- Maybe it would be a good idea to briefly mention what a super-solvent, or super-solvation, is, specially since it's mentioned more than once.
By tracing the formation of product (p-nitrophenol) at different temparature(s), it was discovered that the RDS can change over temparature.
- Maybe this sentence could be rephrased to avoid repeating the word "temperature". Something like By tracing the formation of product (p-nitrophenol), it was discovered that the RDS can change over different temperatures
At higher temparature the RDS is formation of glycosyl enzyme intermediate and at lower temparature the break down of that intermediate.
- It should say At higher temperatures or At a higher temperature.
- In the Koshland Mechanism sub-Section, it is not clear who proposed it first. The beginning of the paragraph introduces the idea of a covalent mechanism as an early debate from Dahlquist. But then it is mentioned that the mechanism was first described by Koshland. Does that mean that the specific mechanism described in the paragraph came from Koshland, but that the notion of a covalent mechanism first came from Dahlquist?
More recently, quantum mechanics/ molecular mechanics (QM/MM) molecular dynamics simulations have been using the crystal structure of HEWL and(to) predict the existence of a covalent intermediate
Evidence for(from) the(no the is needed here) ESI-MS and X-ray structures indicate the existence of a covalent intermediate, but primarily rely on using a less active mutant or non-native substrate.
Imidazole derivatives can form charge-transfer complex with some residues (in or outside active center) to achieve a competitive inhibition of lysozyme.
- It should say "charge-transfer complexes" or "a charge-transfer complex"
Lysozyme exhibits two conformations: an open active state and a closed inactive state
Electronically monitoring the lysozyme showed two conformations, an open active site and a closed inactive site
- This sentence could be changed in order to avoid sounding like a repetition of the beginning of the paragraph.
GomezChristian (talk) 21:16, 2 March 2017 (UTC)
Article Review
INTRO
- I would alter the first two sentences slightly as follows,
Lysozymes, also known as muramidases or N-acetylmuramide glycanhydrolases, are glycoside hydrolases that damage bacterial cell walls by catalyzing the hydrolysis of peptidoglycan.
- Some rewording of the intro paragraph could make the article flow better. For example,
" Peptidoglycan is formed by alternating N-acetylmuramic acid(NAM) and N-acetyl-D-glucosamine (NAG) monomers through β-(1,4) linkages. Lysozymes catalyze hydrolysis of the β-(1,4) lysing the bacteria by compromising the integrity of its cell wall."
Could be changed to something like,
"Peptidoglycan is a polysaccharide consisting of alternating N-acetylmuramic acid(NAM) and N-acetyl-D-glucosamine (NAG) monomers connected through β-(1,4) linkages. Lysozymes catalyze hydrolysis of this linkage thereby lysing the bacteria by compromising the integrity of its cell wall."
- The last sentence about the rate of hydrolysis of chitodextrins is mentioned again in the function section and so can be removed from the intro.
PHYSICAL PROPERTIES
- The physical properties section is very short and seems like it could be placed in the introduction rather than creating a full section for the small but significant paragraph of information.
FUNCTION AND MECHANISM
- In the function section: "the enzyme also can..." to "the enzyme can also..."
- As opposed to saying "it attacks" you could say "hydrolysis takes place"
- Because you have a section devoted to the Phillips mechanism I don't think it's necessary to have the last sentence in the active site section. In addition, I think you could combine the active site and function sections and remove the subheading such that you have somewhat of an intro in the mechanism section and then delve into the various proposed mechanisms.
- The images could be reorganised a bit in this section
Phillips Mechanism
- Spelling mistake: oxo-carbonium should be oxo-carbenium
- In the phillips mechanism section you could show a diagram of the strained char conformation
- Grammar mistake: electrostatically stabilize should be stabilized
- You could add an arrow pushing mechanism showing the stabilisation from the glutamate and aspartate residues and potentially an energy diagram which would also illustrate the RDS.
- You could also expand on the p-nitrophenol study to explain what they were looking for, how they did it and what the key result was.
Koshland Mechanism
- You can reword the first sentence as follows,
" In 1969 Dahlquist proposed a covalent mechanism for lysozyme based on an isotope effect."
- You should refer to your figure in this paragraph when discussing the two different mechanisms
- Some rewording of this paragraph to make it flow better.
- This sentences needs to be reworded
"More recently, quantum mechanics/ molecular mechanics (QM/MM) molecular dynamics simulations have been using the crystal of HEWL and predict the existence of a covalent intermediate"
maybe something as follows, "More recently, quantum mechanics/ molecular mechanics (QM/MM) molecular dynamics simulations have used the crystal structure of HEWL to predict the existence of a covalent intermediate. This is corroborated with ESI-MS data as well as X-Ray crystal structures, however these tend to rely on mutant or non-native substrates."
- You need a citation for the QM/MM work.
Inhibition
- If there is a page for charge-transfer complexes you may want to link it here.
- I'm not sure if this needs its own subheading. This can probably be placed somewhere else in the article.
Enzyme Conformation Changes
- Link to the field effect transistors page.
Alternate Substrates
- This can probably be placed in the intro paragraph to Function and Mechanism.
ROLE IN DISEASE
- --
ROLE IN THERAPY
- This seems to be directly related to the first sentence of the Role in Disease section and so I believe that this can be placed there and remove this section altogether.
HISTORY
- --
CHEMICAL SYNTHESIS
- I also feel that this does not necessarily need its own section despite its significance. It may have a better placement elsewhere in the article
OTHER APPLICATIONS
- --
Overall I think this is a great expansion on an unfortunately short page! The information presented is well cited and in depth, the work is written in an encyclopaedic fashion and besides some small grammatical and aesthetic changes the page looks like its on its to being a great wiki article!