Question

a)Why are transmembrane proteins mostly comprised of alpha helices?

b)More generally, what might happen if you substituted a tryosine for a cystein in the active site of a protein

Answer 1

Answers

a) Transmembrane proteins are mostly comprised of alpha helices because they are mostly polar and are capable of keeping the interaction with hydrophilic molecules continuous. Also the helical structure can satisfy all backbone hydrogen bonds internally, and also does not permit the polar groups to expose to the membrane if the sidechains are hydrophobic. Whereas the beta sheets are mostly involoved in the core of the protein to offer a hydrophobicity in the inner side of the core. Therefore mostly alpha helices make up the transmembrane composition. Another major reason is that the alpha helices are very stable and do not unfold completely under unfavourable conditions like in an elevated temperature facilitated by the helix-coil transition. Since being polar and also being able to undergo structural changes while maintaining integrity. The alpha helices are able to under go mechanical structural changes smoothly therefore allows molecules across the transmembrane and also tolerates low levels of environmental changes.

b) If tryosine is substituted for a cystein in the active site , catalysis gets interrupted or even inhibited. Cystein is a disulphide bridge forming aminoacid whereas tyrosine is an aromatic aminoacid. The active site is designed for specific substrates binding and interaction in nature, this property will change extensivly because of the substitution. For example tyrosine promotes intermolecular thioester formation and is unable to carryout the formation of disulphide bridges like cysteine, hence when substituted with cystein the whle active site dynamics will change. Sometimes the active site loses its stability altogether because the cysteine residues offer a greater stability in comparison to tyrosin. In exceptionally unique cases the substitution might improve the substrate binding which is in reality rare.