Difference between revisions of "Structure-based mutation analysis ARSA"

From Bioinformatikpedia
(→‎Mutation 1)
(→‎Mutation 1)
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| Phe -Val
 
| Phe -Val
 
| 356
  
| 356
−
|[[Image:arsa_hydro356.png|thumb|150px|]]
 +
|[[Image:arsa_hydro356.png|200px|]]
−
|[[Image:arsa_scwrl_hydro356.png|thumb|]]
 +
|[[Image:arsa_scwrl_hydro356.png|200px|]]
−
|[[Image:arsa_both356.png|thumb|150px|Reference and mutated amino acid]]
 +
|[[Image:arsa_both356.png|200px]]
 
|-
  
|-
 
| 7
  
| 7
 
| Thr-Ile
 
| Thr-Ile
 
| 409
  
| 409
−
|[[Image:arsa_hydro409.png|thumb|150px|]]
 +
|[[Image:arsa_hydro409.png|200px|]]
−
|[[Image:arsa_scwrl_hydro409.png|thumb|]]
 +
|[[Image:arsa_scwrl_hydro409.png|200px|]]
−
|[[Image:arsa_both409.png|thumb|150px|Reference and mutated amino acid]]
 +
|[[Image:arsa_both409.png|200px]]
 
|-
  
|-
 
| 8
  
| 8
 
| Asn-Ser
 
| Asn-Ser
 
| 440
  
| 440
−
|[[Image:arsa_hydro440.png|thumb|150px|]]
 +
|[[Image:arsa_hydro440.png|200px|]]
−
|[[Image:arsa_scwrl_hydro440.png|thumb|]]
 +
|[[Image:arsa_scwrl_hydro440.png|200px]]
−
|[[Image:arsa_both440.png|thumb|150px|Reference and mutated amino acid]]
 +
|[[Image:arsa_both440.png|200px]]
 
|-
  
|-
 
| 9
  
| 9
 
| Cys-Gly
 
| Cys-Gly
 
| 489
  
| 489
−
|[[Image:arsa_hydro489.png|thumb|150px|]]
 +
|[[Image:arsa_hydro489.png|200px|]]
−
|[[Image:arsa_scwrl_hydro489.png|thumb|]]
 +
|[[Image:arsa_scwrl_hydro489.png|200px|]]
−
|[[Image:arsa_both489.png|thumb|150px|Reference and mutated amino acid]]
 +
|[[Image:arsa_both489.png|200px]]
 
|-
  
|-
 
| 10
  
| 10
 
| Arg-His
 
| Arg-His
 
| 496
  
| 496
−
|[[Image:arsa_hydro496.png|thumb|150px|]]
 +
|[[Image:arsa_hydro496.png|200px|]]
−
|[[Image:arsa_scwrl_hydro496.png|thumb|]]
 +
|[[Image:arsa_scwrl_hydro496.png|200px|]]
−
|[[Image:arsa_both496.png|thumb|150px|Reference and mutated amino acid]]
 +
|[[Image:arsa_both496.png|200px]]
 
|-
  
|-
 
|}
  
|}

Revision as of 14:42, 30 June 2011

Preparation

Visualization with Pymol

The following image shows a pymol visualization of Arylsulfatase A, together with all known active and binding sites.

Pymol visualization of ARSA (with closed gaps). The active site is depicted in yellow, metal-binding site in blue, substrate binding sites in green and missense mutations in red.

One can see, that the mutations are spread out through the protein. Some lie near functional sites, other are very distant from them. The table below shows again Pymol visualizations of all mutations, but each seperately. With this, we want to try to derive investigate the correlation of location of the mutation with respect to functional sites and its effect on the protein function.

Nr. mutation position Pymol image Description Effect on function
1 Asp-Asn 29
Arsa29.png
The mutation is located at the position of a metal-binding site. harmful
2 Pro - Ala 136
Arsa136.png
The mutation is located near the active site and a substrate binding site in sequence as well as in structure. harmful
3 Gln-His 153
Arsa153.png
The mutation is located near the active site and a substrate binding site in sequence as well as in structure. harmful
4 Trp-Cys 193
Arsa193.png
The mutation is at moderate distance to all important functional sites of the protein. neutral
5 Thr-Met 274
Arsa274.png
The mutation is located very distant from the active site and a substrate binding site in sequence as well as in structure.
It is located within a beta sheet. 		harmful
6 Phe -Val 356
Arsa356.png
The mutation is at moderate distance to all important functional sites of the protein. neutral
7 Thr-Ile 409
Arsa409.png
The mutation is not close to important functional sites. harmful
8 Asn-Ser 440
Arsa440.png
The mutation is very distant from all functional sites. neutral
9 Cys-Gly 489
Arsa489.png
The mutation is very distant from all functional sites. harmful
10 Arg-His 496
Arsa496.png
The mutation is very distant from all functional sites. harmful

Above visualizations indicate, that mutations near functional important sites of the protein are likely to cause a harmful effect. However, for distant mutations no trend can be observed.

SCRWL

First, we extracted the amino acid sequence from our pdb file and converted it to lower case. 


repairPDB arsa_model.pdb -seq > arsa.model.seq
tr '[:upper:]' '[:lower:]' < arsa.model.seq > arsa.model.lower.seq

Next, we included the individual mutations as capital letters in seperate files and executed scwrl with the following command: 


scwrl cmd
Mutation 1
Nr. mutation position Reference amino acid mutated amino acid both
1 Asp-Asn 29 Arsa hydro29.png Arsa scwrl hydro29.png Arsa both29.png
2 Pro - Ala 136 Arsa hydro136.png Arsa scwrl hydro136.png Arsa both136.png
3 Gln-His 153 Arsa hydro153.png Arsa scwrl hydro153.png Arsa both153.png
4 Trp-Cys 193 Arsa hydro193.png Arsa scwrl hydro193.png Arsa both193.png
5 Thr-Met 274 Arsa hydro274.png Arsa scwrl hydro274.png Arsa both274.png
6 Phe -Val 356 Arsa hydro356.png Arsa scwrl hydro356.png Arsa both356.png
7 Thr-Ile 409 Arsa hydro409.png Arsa scwrl hydro409.png Arsa both409.png
8 Asn-Ser 440 Arsa hydro440.png Arsa scwrl hydro440.png Arsa both440.png
9 Cys-Gly 489 Arsa hydro489.png Arsa scwrl hydro489.png Arsa both489.png
10 Arg-His 496 Arsa hydro496.png Arsa scwrl hydro496.png Arsa both496.png
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