Passion to Compassion: PAH-gene-Versus-PAH

A narrative blog post which includes an original description of the allele and a discussion of the impact of the change on the predicted secondary structure.

0.0001 PHENYLKETONURIA

PAH, IVS12DS, G-A, +1

The first PKU mutation identified in the PAH gene was a single base change (GT-to-AT) in the canonical 5-prime splice donor site of intron 12.

Since the variant/allele 0.0001 is due to the single base change in the site of intron 12, I picked the allele 0.0002 and discussed the impact on the predicted secondary structure.

0.0002 PHENYLKETONURIA

PAH, ARG408TRP

This defect is caused by a CGG-to-TGG transition in exon 12, resulting in an amino acid substitution (arg-to-trp) at residue 408 (R408W) of PAH.

This mutation makes up about 20% of the mutant PAH genes. It is one of the examples of CpG mutation. The R408W mutation occurs within the catalytic domain of PAH. PAH with the R408W mutation formed high-molecular-mass aggregates, indicative of severe distortion of the protein's oligomeric state.

I opened the mRNA sequence of my PAH gene in the seq-builder and highlighted the open reading frame of the gene beginning with the ATG codon of methionine. I highlighted the ORF in the upper strand and translated it into the protein sequence and saved it.
Since the allelic/variant is the change in the amino acid Arginine to(R) to tryptophan (W), I opened the protein sequence in the edit seq made the change and saved it under the name of PAH-allele(R408W).
The Arginine is a basic amino acid and tryptophan is a hydrophobic amino acid thus I expect to see changes in the secondary structure.

The protein statistics in the edit-seq about the PAH-gene and the PAH-allele is different in the molecular weight, isoelectric point to PH.
The PAH-gene Protein statistics.
    Molecular Weight 51862.15 Daltons
    452 Amino Acids
    54 Strongly Basic(+) Amino Acids (K,R)
        60 Strongly Acidic(-) Amino Acids (D,E)
        155 Hydrophobic Amino Acids (A,I,L,F,W,V)
        119 Polar Amino Acids (N,C,Q,S,T,Y)
        6.408 Isolectric Point
        -4.147 Charge at PH 7.
    Protein Info about pah-allele-R-W.pro(1,453)
          Molecular Weight 51892.17 Daltons
       452 Amino Acids
      53 Strongly Basic(+) Amino Acids (K,R)
        60 Strongly Acidic(-) Amino Acids (D,E)
        119 Polar Amino Acids (N,C,Q,S,T,Y)
      6.293 Isolectric Point
     -5.147 Charge at PH 7.0

The changes seen in the Protean of DNASTAR are as following:

The Beta Regions from the amino acid 400 till the end of the secondary structure as depicted by the Garnier-Robson and Chou- Fasman algorithm. The turn regions by the Chou-Fasman algorithm. The coil region by the Garnier-Robson algorithm the alpha amphipathic region and the Beta Amphipathic region as well as the flexible regions by Karplus-Schulz algorithm.
I have observed changes in the Apha, beta coil and turn regions by the Chou-Fasman and Garnier-Robonson as seen in the zoomed version of the Protean in DNASTAR.

The PAH-gene-&&-PAH-allele(R408W)

The detalied comparison of the PAH gene and its allele with (R408W) in Protean.

The changes seen in the region from amino acid 400 to the end of the polymer for the PAH gene and the allele variant in Protean. The Amino Acids from 400 to 420 are highlighted.

PAH-gene-400-420AA

PAH-allele(R408W)-400-420AA

The secondary structure changes as seen in the Protean 3D of DNASTAR in the PAH-gene and PAH-alllele (R408W).

Secondary Structure - Garnier-Robson—Examines the propensity of a given residue to exist in a certain structure.
I observed the changed in the beta regions, turn regions and coil regions in PAH-gene and allele but no change in the alpha regions.