Difference between revisions of "Structure-based mutation analysis (PKU)"

From Bioinformatikpedia
(Mutations)
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</div>
 
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== Mutations ==
 
== Mutations ==
As you probably know from [[Predicting_the_Effect_of_SNPs_(PKU)#Our dataset|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.
+
As you probably know from [[Predicting_the_Effect_of_SNPs_(PKU)#Our dataset|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.<br>
  +
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.
  +
<div style="float: center; width: 100%">
  +
{| align="center"
  +
!| SNP
  +
!| effect
  +
!| prediction
  +
!| validation
  +
  +
|-
  +
|[[#ARG158GLN|ARG158GLN]]
  +
| disease causing
  +
|
  +
|[[File:unknown.jpeg|25px|center]]
  +
|-
  +
|[[#GLN172HIS|GLN172HIS]]
  +
| non-disease
  +
|
  +
|[[File:unknown.jpeg|25px|center]]
  +
|-
  +
|[[#ARG243GLN|ARG243GLN]]
  +
| disease causing
  +
|
  +
|[[File:unknown.jpeg|25px|center]]
  +
|-
  +
|[[#LEU255SER|LEU255SER]]
  +
| disease causing
  +
|
  +
|[[File:unknown.jpeg|25px|center]]
  +
|-
  +
|[[#MET276VAL|MET276VAL]]
  +
| non-disease
  +
|
  +
|[[File:unknown.jpeg|25px|center]]
  +
|-
  +
|[[#ARG297CYS|ARG297CYS]]
  +
| disease causing
  +
|
  +
|[[File:unknown.jpeg|25px|center]]
  +
|-
  +
|[[#ALA322GLY|ALA322GLY]]
  +
| hyperphenylalaninemia
  +
|
  +
|[[File:unknown.jpeg|25px|center]]
  +
|-
  +
|-
  +
|[[#GLU330ASP|GLU330ASP]]
  +
| disease causing
  +
|
  +
|[[File:unknown.jpeg|25px|center]]
  +
|[[#GLY337VAL|GLY337VAL]]
  +
| disease causing
  +
|
  +
|[[File:unknown.jpeg|25px|center]]
  +
|-
  +
|[[#ARG408TRP|ARG408TRP]]
  +
| disease causing
  +
|
  +
|[[File:unknown.jpeg|25px|center]]
  +
|}
  +
  +
</div>

Revision as of 13:39, 20 June 2012

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">

Table with results from UNIProt with r-Value inserted
Entry Method Resolution (Å) r-Value Chain Positions PDBsum
1DMW X-ray 2.00 0.200 A 118-424 [»]
1J8T X-ray 1.70 0.197 A 103-427 [»]
1J8U X-ray 1.50 0.157 A 103-427 [»]
1KW0 X-ray 2.50 0.220 A 103-427 [»]
1LRM X-ray 2.10 0.211 A 103-427 [»]
1MMK X-ray 2.00 0.199 A 103-427 [»]
1MMT X-ray 2.00 0.213 A 103-427 [»]
1PAH X-ray 2.00 0.176 A 117-424 [»]
1TDW X-ray 2.10 0.206 A 117-424 [»]
1TG2 X-ray 2.20 0.213 A 117-424 [»]
2PAH X-ray 3.10 0.251 A/B 118-452 [»]
3PAH X-ray 2.00 0.175 A 117-424 [»]
4ANP X-ray 2.11 0.204 A 104-427 [»]
4PAH X-ray 2.00 0.169 A 117-424 [»]
5PAH X-ray 2.10 0.163 A 117-424 [»]
6PAH X-ray 2.15 0.171 A 117-424 [»]

</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.

1J8U

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.

<figure id="1J8Uwhole">
Rendering of the overall structures of 1J8U using PyMol. The protein is colored cyan overall, whereas the Fe-atom is colored red and the important residues are shown as sticks and colored in the element-based fashion. Binding is shown with yellow strokes, if the distance is bigger than 1.5 Å
</figure>
<figure id="1J8Uclose">
Rendering of a close-up of the structures of 1J8U using PyMol. The protein is colored cyan overall, whereas the Fe-atom is colored red and the important residues are shown as sticks and colored in the element-based fashion. Binding is shown with yellow strokes, if the distance is bigger than 1.5 Å
</figure>

Mutations

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.

SNP effect prediction validation
ARG158GLN disease causing
Unknown.jpeg
GLN172HIS non-disease
Unknown.jpeg
ARG243GLN disease causing
Unknown.jpeg
LEU255SER disease causing
Unknown.jpeg
MET276VAL non-disease
Unknown.jpeg
ARG297CYS disease causing
Unknown.jpeg
ALA322GLY hyperphenylalaninemia
Unknown.jpeg
GLU330ASP disease causing
Unknown.jpeg
GLY337VAL disease causing
Unknown.jpeg
ARG408TRP disease causing
Unknown.jpeg