Difference between revisions of "Fabry:Structure-based mutation analysis"

From Bioinformatikpedia
(→‎Preparation: correct positions)
(→‎Preparation)
Line 13: Line 13:
 
! style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 2px 0;"| PDB
  
! style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 2px 0;"| PDB
 
! style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 2px 0;"| R-factor
  
! style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 2px 0;"| R-factor
  +
! style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 2px 0;"| R-free
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 1R46
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 1R46
Line 22: Line 23:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=1R46 [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=1R46 [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.262
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.262
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.301
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 1R47
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 1R47
Line 31: Line 33:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=1R47 [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=1R47 [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.285
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.285
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.321
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3GXN
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3GXN
Line 40: Line 43:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3GXN [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3GXN [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.239
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.239
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.301
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3GXP
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3GXP
Line 49: Line 53:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3GXP [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3GXP [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.204
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.204
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.265
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3GXT
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3GXT
Line 58: Line 63:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3GXT [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3GXT [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.245
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.245
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.306
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3HG2
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3HG2
Line 67: Line 73:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3HG2 [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3HG2 [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.178
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.178
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.202
 
|-
 
|-
−
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;" | '''3HG3'''
 +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| '''3HG3'''
−
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;" | '''X-ray'''
 +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| '''X-ray'''
−
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;" | '''1.90'''
 +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| '''1.90'''
−
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;" | '''A/B'''
 +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| '''A/B'''
−
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;" | '''32-426'''
 +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| '''32-426'''
−
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;" | [http://www.ebi.ac.uk/pdbsum/3HG3 [»]]
 +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.ebi.ac.uk/pdbsum/3HG3 [»]]
−
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;" | [http://www.pdb.org/pdb/explore/explore.do?structureId=3HG3 [»]]
 +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3HG3 [»]]
−
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;" | '''0.167'''
 +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| '''0.167'''
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| '''0.197'''
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3HG4
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3HG4
Line 85: Line 93:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3HG4 [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3HG4 [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.166
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.166
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.221
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3HG5
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3HG5
Line 94: Line 103:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3HG5 [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3HG5 [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.192
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.192
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.227
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3LX9
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3LX9
Line 103: Line 113:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3LX9 [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3LX9 [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.178
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.178
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.218
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3LXA
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3LXA
Line 112: Line 123:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3LXA [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3LXA [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.216
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.216
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.244
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3LXB
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3LXB
Line 121: Line 133:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3LXB [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3LXB [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.227
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.227
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.264
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3LXC
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3LXC
Line 130: Line 143:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3LXC [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3LXC [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.186
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.186
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.237
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3S5Y
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3S5Y
Line 139: Line 153:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3S5Y [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3S5Y [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.195
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.195
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.230
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3S5Z
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3S5Z
Line 148: Line 163:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3S5Z [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3S5Z [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.211
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.211
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.234
 
|-
  
|-
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3TV8
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 3TV8
Line 157: Line 173:
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3TV8 [»]]
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| [http://www.pdb.org/pdb/explore/explore.do?structureId=3TV8 [»]]
 
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.203
  
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.203
  +
| style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| 0.239
 
|-
  
|-
 
|}
  
|}

Revision as of 20:53, 20 June 2012

Preparation

<figtable id="tab:Prep"> All available PDB structures assigned to the Uniprot entry P06280 along with the according Resolution,
Coverage and R-factor. The R-factor was obtained from the PDBsum page. The chosen structure 3HG3 is highlighted.

Entry Method Resolution (Å) Chain Positions (up to 429) PDBsum PDB R-factor R-free
1R46 X-ray 3.25 A/B 32-422 [»] [»] 0.262 0.301
1R47 X-ray 3.45 A/B 32-422 [»] [»] 0.285 0.321
3GXN X-ray 3.01 A/B 32-421 [»] [»] 0.239 0.301
3GXP X-ray 2.20 A/B 32-422 [»] [»] 0.204 0.265
3GXT X-ray 2.70 A/B 32-422 [»] [»] 0.245 0.306
3HG2 X-ray 2.30 A/B 32-422 [»] [»] 0.178 0.202
3HG3 X-ray 1.90 A/B 32-426 [»] [»] 0.167 0.197
3HG4 X-ray 2.30 A/B 32-423 [»] [»] 0.166 0.221
3HG5 X-ray 2.30 A/B 32-422 [»] [»] 0.192 0.227
3LX9 X-ray 2.04 A/B 32-422 [»] [»] 0.178 0.218
3LXA X-ray 3.04 A/B 32-426 [»] [»] 0.216 0.244
3LXB X-ray 2.85 A/B 32-427 [»] [»] 0.227 0.264
3LXC X-ray 2.35 A/B 32-422 [»] [»] 0.186 0.237
3S5Y X-ray 2.10 A/B 32-422 [»] [»] 0.195 0.230
3S5Z X-ray 2.00 A/B 32-421 [»] [»] 0.211 0.234
3TV8 X-ray 2.64 A/B 32-422 [»] [»] 0.203 0.239

</figtable>

We chose to use the structure 3HG3, since it has the best resolution (1.90 Å) and the second best R-factor (see <xr id="tab:Prep"/>). The best R-factor, which is a measure of the agreement between the crystallographic model and the experimental X-ray diffraction data <ref>R-factor (crystallography) (May 17, 2012‎) http://en.wikipedia.org/wiki/R-factor_%28crystallography%29, June 20, 2012</ref>, could be achieved with the structure 3HG4, but it has a resolution of 2.30 Å and hence we decided to use 3HG3. All structures cover the protein completely except for the signal peptide from position 1 to 31.

Vizualisation

<figure id="fig:allSNPs">

All SNPs mapped onto the structure 3HG3. Mutated sites are shown in blue. The active site (residues 170 and 231) is shown in pink, substrate binding site (position 203-207) in cyan and the existing five disulfide bonds (52 ↔ 94, 56 ↔ 63, 142 ↔ 172, 202 ↔ 223, 378 ↔ 382) are highlighted in yellow

</figure>


Create mutation

SCWRL


Comparison energies

foldX

Minimise

Gromacs

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