Suppose that you are studying the interactions between the substrate and the enz

Question

Suppose that you are studying the interactions between the substrate and the enzyme above. It is possible to make variant enzymes that differ from the one above by a single amino acid substitution. (For example, Asp 78 could be replaced with tryptophan). You could use this technique to investigate the roles of each amino acid shown above.

i) If you change Arg 31 to a lysine, would you predict that the substrate still binds, or that the substrate now fails to bind to the altered enzyme? Explain.

ii) Choose an amino acid substitution for Ser 161.

iii) Explain the possible outcome of this change.

Note: There are many possible correct answers for (ii) and (iii). A table of amino acid structures can be found at the end of this exam.

Shown below is a close up of a substrate CUDP-Glucose) bound to the active site of an enzyme UTase). The shaded area is the en e: the structure of the substrate is shown. Ser161 CH2OH H O. H O O OH H CH2 P-o-P OH OH OH OH Arg 31 Two amino acids of the enzyme are highlighted: Arg 31 and Ser 161.

Explanation / Answer

Ans. 1. Yes

Note the position of Arg 31, it interacts with two negatively charged O-atoms.

Arginine is a basic amino acid, and is positively charged at physiological pH. Similar to Arg, Lysine is also a basic amino acid and is positively charged.

Therefore, owing to similarity with Arg31 in terms of charge and polarity, the substituted lysine residue is most likely to exhibit binding with two negatively charged O-atoms of the substrate through ionic interactions.   

Note: Histidine is also a basic, positively charged amino acid. However, the side chain of arginine is more similar to lysine (both the aliphatic) than that of histidine (with pentacyclic side chain). Therefore, stearic hindrance, accounting group projection for appropriate proximity, and aliphatic nature of side chain, lysine is a better substitute to arginine than histidine.

#2. Serine has a catalytic -OH group in its side chain. The other only amino acid with catalytic -OH group is threonine. Thus, serine can be substituted with threonine.

Note: Tyrosine also has a -OH group in its side chain. However, the -OH group is linked to a phenyl group in the side chain.

Side chain of both serine and threonine are aliphatic and differ in length by 1C (serine being smaller). Whereas the side chain of tyrosine is aromatic and bulky with respect to that of serine or threonine.

Therefore, accounting stearic hindrance, group projections for proximity and aliphatic side chain of serine, the threonine residue is a better substitute than tyrosine.

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