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Phenylalanine hydroxylase (PAH)

Part Description

Phenylalanine hydroxylase (PAH) gene is the part responsible for providing instructions to make phenylalanine hydroxylase enzyme. this enzyme is responsible for hydroxylating phenylalanine and turning it to tyrosine in the presence of tetrahydrobiopterin (BH4). and as phenylalanine is present in almost all proteins and some artificial sweeteners this process of hydroxylation is really important to prevent its' accumulation.
also the product of tyrosine is used to make various homones and neurotransmitters.

Usage

PAH is a Member of the hydroxylase enzymes in the human body and it processes phenylalanine to be hydroxylated in order to produce tyrosine. PAH is a hydroxylase that needs biopterin that convert phenylalanine to tyrosine and in case of its absence or deficiency lead to a metabolic condition called Phenylketonuria that can occur in humans due to abnormalities in the gene that codes for it so we use this part to replace the deficient one and process phenylalanine into tyrosine

Characterization of Mutational Landscape

After creating a multiple sequence alignment of the protein sequence and predicting mutational landscapes, the effect of these mutations on the evolutionary fitness of the protein is tested. The prediction of the mutational landscape by saturation mutagenesis of the PAH protein. The (G183E) mutation, as depicted in the chart, had the greatest score when compared to other mutations. On the other hand, it's clear that the (M180E) had the least evolutionary fitness for PAH protein. As displayed in Figure(1)

Figure 1. (shows the mutational landscape of the PAH protein.)

References

Sequence and Features