Special Topics 1 - Alanine Question

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Name _____Jiachen Liu________student #________1003744066____________PRA ___9114_____
Bio 206 - Special Topics 1: Question
As illustrated for naturally occurring haemoglobin (see lecture 6, slide 16), the substitution of one amino acid for another (i.e. Glu to Val) can have dramatic effects on the functioning of a protein and long-range effects on cell structure. Consequently, molecular biologists use single amino acid substitutions as an experimental approach to determine if a particular amino acid plays a crucial role in the functioning of a particular protein of interest. Most often, alanine is the amino acid that is used as the “first choice” substitute for a naturally occurring amino acid in the primary sequence of the protein. What properties of alanine make it the amino acid of choice for this purpose? 
Alanine was widely used in scanning mutagenesis technique to determine the function or stability of specific amino acid residues to the given protein.1 Alanine was chosen as the substitution to the primary sequence in the protein for several reasons. Firstly, alanine represents a deletion of the beta-carbon side chain yet not affect the conforming of the main chain. Secondly, the proper size and non-polar properties of alanine ensure it is physicochemically innocuous to the rest structure of the protein.3 Furthermore, alanine as the second most abundant amino acid in the natural sequence which meets the secondary structure preference of other amino acid process.3 Thirdly, the methyl side-chain of alanine is non-reactive that hardly involves in the protein function which minimize the overall affect of substitution brings to the original protein function.2 Overall, the alanine was used as the first choice for the scanning mutagenesis because it’s non-polar property, chemically inert and none-reactive methyl side chain that minimize the overall affect of substitution brings to the other amino residues of the protein. And allows researcher to investigate the specific function of the amino acid residues that is substituted by the alanine.
Reference: 
1. Morrison KL, Weiss GA (June 2001). "Combinatorial alanine-scanning". Curr Opin Chem Biol. 5 (3): 302–7. doi:10.1016/S1367-5931(00)00206-4. PMID 11479122
2. Textbook of Biotechnology. McGraw-Hill Education (I). 2012. ISBN 9780071070072.
3. Gray, V. E., Hause, R. J., & Fowler, D. M. (2017). Analysis of Large-Scale Mutagenesis Data To Assess the Impact of Single Amino Acid Substitutions. Genetics, 207(1), 53-61. doi:10.1534/genetics.117.300064