[skk_l]

Question 1
a. Why cannot hydrogen bonding explain why proteins fold in an aqueous
environment? What does cause proteins to fold? [5 marks];

b. What is a hydrogen bond? What role does it have in the secondary structures of
proteins? Illustrate your answer for two types of secondary structure [8 marks];

c. How can knowledge of protein structure help in the design of new drugs? [4 marks];

d. Draw the mechanism of hydrolysis of an amide bond by a serine protease. Why is
the enzyme critical to this hydrolysis? [8 marks].


I am really struggling in answering these questions and would like some help.

[JMaydom]

I'm no expert as I'm a chemist not a biochemist but here goes!

a. In an aqueous environment the protein can hydrogen bond perfectly adequately to the water molecules, other types of bonding such as disulphide bridges are important.
Folding is also promoted by hydrophobic interactions as the 'greasy' parts of the molecule want to retreat to the center of the protein.

b. Interaction between a atom with a delta + and a delta - charge...... eg.

N-H ////// O-H

Basically an electrostatic interaction! On a higher level there are some molecular orbital considerations which predict the strongest hydrogen bonding when the angle between the N, H and O is 180 degrees.

c. YES!!! Lots of drugs work by blocking the active site of enzymes. Molecules can be tailored to fit the gap increasing selectivity and potency.

d. Sorry, not studied this I would expect this mechanism is somewhere online

[Alchem]

[QUOTE=skk_l;38697798]Question 1


d. Draw the mechanism of hydrolysis of an amide bond by a serine protease. Why is the enzyme critical to this hydrolysis? [8 marks].

I don't remember the exact details, but the following mechanism is approximately valid:

The hydroxyl group of the serine moity (from the protease molecule) acts as a nucleophile and forms a temporary bond with the carbonyl carbon, the carbonyl oxygen developing a -ve charge . Thus a tetrahedral transition state is generated.

Next, the oxygen from a water molecule attaches to the carbonyl carbon (which is now tetrahedral), and the bond between the serine hydroxyl and the carbonyl carbon is broken simultaneously. Thus, the enzyme molecule is regenerated here, and is ready for further catalysis.

Finally, the bound water molecule loses an H⁺ , the -NH₂ group gets detached as NH₃ , and the carbonyl oxygen re-establishes a double bond with the carbon. Thus, the corresponding carboxylic acid is formed.

Essentially, this reaction is a Substitution Nucleophilic Bimolecular, with the enzyme serine hydroxyl acting as the initial (temporary) nucleophile, and a water molecule acting as the final nucleophile.

Unfortunately, I don't see the means here to draw the reaction scheme, otherwise things would have been a bit clearer. Hopefully though, this verbal explanation would help.

[skk_l]

[QUOTE=Alchem;38724873]

(Original post by skk_l)
Question 1


d. Draw the mechanism of hydrolysis of an amide bond by a serine protease. Why is the enzyme critical to this hydrolysis? [8 marks].

I don't remember the exact details, but the following mechanism is approximately valid:

The hydroxyl group of the serine moity (from the protease molecule) acts as a nucleophile and forms a temporary bond with the carbonyl carbon, the carbonyl oxygen developing a -ve charge . Thus a tetrahedral transition state is generated.

Next, the oxygen from a water molecule attaches to the carbonyl carbon (which is now tetrahedral), and the bond between the serine hydroxyl and the carbonyl carbon is broken simultaneously. Thus, the enzyme molecule is regenerated here, and is ready for further catalysis.

Finally, the bound water molecule loses an H⁺ , the -NH₂ group gets detached as NH₃ , and the carbonyl oxygen re-establishes a double bond with the carbon. Thus, the corresponding carboxylic acid is formed.

Essentially, this reaction is a Substitution Nucleophilic Bimolecular, with the enzyme serine hydroxyl acting as the initial (temporary) nucleophile, and a water molecule acting as the final nucleophile.

Unfortunately, I don't see the means here to draw the reaction scheme, otherwise things would have been a bit clearer. Hopefully though, this verbal explanation would help.

Thx a lot

[illusionz]

(Original post by skk_l)
Question 1
a. Why cannot hydrogen bonding explain why proteins fold in an aqueous
environment? What does cause proteins to fold? [5 marks]

Because the unfolded protein can form hydrogen bonds to water, hence it is H bonded in both the natured and denatured state. However, there is a massive massive entropic gain in folding because of all the water released. As you should know,

dG = dH - TdS, so with a large positive dS, you get a nice negative dG and hence it is favourable.

It's a pretty basic explanation but should help.