Structure-based mutation analysis (PKU)
short task description
Finding the right structure
As proposed we searched the UNIProt entry for our protein and then selected the entry with the highest resolution and the lowest r-Value. In our case this is 1J8U which is the protein in a complex with its cosubstrate BH4. IN the following we will only use this structure, but we also list the results we found. <figtable id="uniprotresult">
</figtable> In <xr id="uniprotresult"/> there are all results according to which we selected 1J8U to be our reference for this weeks task. The corresponding line is marked in yellow.
In order to know the structure of the protein and its important residues, we have a look at its structure with PyMol and visualize the BH4 and the Fe-ion with the most important residues.
As you probably know from last weeks dataset the first two mutations are located before residue 103 and therefore not contained in the structure. We will change them according to the premise, that the number of diseasecausing and non-diseasecausing mutations are equal.
We propose the following dataset, chosen mostly from well known SNPs from OMIM. They include mutations causing no reported effect, the mild related hyperphenylalaninemia (reduced activity, but functional enzyme) and phenylketonuria.