Rs121907968
Contents
General Information
| SNP-id | rs121907968 |
| Codon | 485 |
| Mutation Codon | Trp -> Arg |
| Mutation Triplet | gTGG -> CGG |
Pysicochemical Properities
First of all, we explored the amino acid properties and compared them for the original and the mutated amino acid. Therefore we created the possible effect that the mutation could have on the protein.
| Trp | Arg | consequences |
| aromatic, polar, hydrophobic, neutral | positive charged, polar, hydrophilic | Trp is very big, because of two aromatic rings in its structure. Furthermore, it is hydrophobic, whereas, Arg is a hydrophilic amino acid. Therefore, the changes in the 3D structure might be extreme and delete the function of the protein. |
Visualisation of the Mutation
In the next step, we created the visualization of the muation with PyMol. Therefore we created a picture for the original amino acid, for the new mutated amino acid and finally for both together in one picture whereas the mutation is white colored. The following pictures display that the mutated amino acid Arginine looks very different to Tryptophan. Tryptophan has two huge aromatical rings. Contrary, Aspartate is also a long amino acid and forks at the end of the rest. Furthermore, Arginige is also orientated in a completly different direction. Because of the aromatical rings the differences between these two amino acids is realy huge. Therefore, the amino acids will probably cause drastical effects on protein structure and function.
| picture original aa | picture mutated aa | combined picture |
Subsitution Matrices Values
| PAM 1 | Pam 250 | BLOSOUM 62 | ||||||
| value aa | most frequent substitution | rarest substitution | value aa | most frequent substitution | rarest substitution | value aa | most frequent substitution | rarest substitution |
| 2 | 2 (Arg) | 0 (all, except Arg, Phe, Ser, Tyr) | 2 | 2 (Arg) | 0 (all, except Arg, His, Leu, Phe, Ser, Tyr) | -3 | 2 (Tyr) | -4 (Asn, Asp, Pro) |
PSSM analysis
| self-information | expected self-information | |
| Trp | 13 | 99 |
| Arg | -6 | 0 |
Conservation Analysis with Multiple Alignments
As a next step we created a multiple alignment which contains the HEXA sequence and 9 other mammalian homologous sequences from uniprot. Afterwards we looked at the position of the different mutations and looked at the conservation level on this position. The regarded mutation is presented by the colored column. Here we can see, that the all other mammalians have also on this position the amino acid Tryptophan. Therefore, the mutation on this position is highly conserved and a mutation there will cause probably huge structural and functional changes for the protein.
Secondary Structure Mutation Analysis
As a next step we compared the different results of the secondary structure prediction tools JPred and PsiPred. Afterwards we can examine in which secondary structure element and where therein the mutation takes place. This can give an overview of how drastical the mutation can be. In this case both tools agree and predict at the position of the mutation a coil. This has a result, that the mutation at this position would not destroy or split a secondary structure element. It will probably only changes the coil between two secondary structure elements, but this can sometimes also cause a change of the the following secondary structure. We think that a drastical change of the protein structure and its function is unlikly because the mutation does not affect a secondary struture element. The change of the coil will probably only take places between two secondary structure elements which will probably not change the protein.
JPred: ...HHHHCCCCCCCCHHHHHHHHHHHHHHHHHCCCCCCCCCCCCCCHHHCCC... PsiPred: ...HHHCCCCCCCCCHHHHHHHHHHHHHHHHHCCCCCCCCCCCCCCCCCCCC...
Comparison with the real Structure:
Afterwards we also visualize the position of the muation (red) in the real 3D-structure of PDB and compare it with the predicted secondary structure. The visualisation can therefore like above the predicted secondary structure display if the mutation is in a secondary structure element or in some other regions.
Here in this case the mutationposition disagree with the position of the predicted secondary structure and is within a alpha-helices. This means a mutation will probably destroy or split the alpha helix which affects drastical structural changes on the protein. We think that a structural change is very likely, because it is within a secondary structure element and will therefore cause extrem changes.
SNAP Prediction
| Substitution | Prediction | Reliability Index | Expected Accuracy |
| R | Non-neutral | 7 | 96% |
A detailed list of all possible substitutions can be found [here]
SIFT Prediction
SIFT Matrix:
Each entry contains the score at a particular position (row) for an amino acid substitution (column). Substitutions predicted to be intolerant are highlighted in red.
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SIFT Table
Threshold for intolerance is 0.05.
Amino acid color code: nonpolar, uncharged polar, basic, acidic.
Capital letters indicate amino acids appearing in the alignment, lower case letters result from prediction.
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