Structure-based mutation analysis Gaucher Disease

From Bioinformatikpedia
Revision as of 18:20, 21 June 2012 by Angermue (talk | contribs)

Cystral structure

<figtable id="tab:mutations">

PDB Res [Å] R value Coverage pH
2nt0 1.80 0.18 96% (40-536) 4.5
3gxi 1.84 0.19 96% (40-536) 5.5
2v3f 1.95 0.15 96% (40-536) 6.5
2v3d 1.96 0.16 96% (40-536) 6.5
1ogs 2.00 0.18 96% (40-536) 4.6

The 5 crystral structures of glycosylceramidase with the highest resolution. The physiological lysosomal pH value is 4.5. 2nt0 was selected for the analysis. </figtable>

Mutations

<figtable id="tab:mutations">

Nr Pos
P04062
Pos
2nt0_A
From To Disease
causing
1 99 60 H R No
2 211 172 V I No
3 150 111 E K Yes
4 236 197 L P Yes
5 248 209 W R Yes
6 509 470 L P No
7 351 312 W C Yes
8 423 384 A D Yes
9 482 443 D N No
10 83 44 R S No

Mutations used for the structure-based mutation analysis. </figtable>

<figure id="fig:mutations">

2nt0_A with the selected mutations of <xr id="tab:mutations"/>. Blue: wildtype residues; Red: mutant residues; Orange: active site residues E235 and E340.

</figure>

SCWRL

<figure id="fig:scwrl">

SNPs of <xr id="tab:mutations"/> introduced by SCWRL. Blue: wildtype residue; Red: mutant residue. </figure>

<figtable id="tab:scwrl">

Nr Mutation Wildtype Mutatant Clashes Structural
change
H-bonds Hydrophobicity H-bonds Hydrophobicity
1 H60R T471 Hydrophilic G62 Hydrophilic No No
2 V172I Hydrophobic Hydrophobic No No
3 E111K Hydrophilic Hydrophilic No No
4 L197P Hydrophobic Hydrophobic No No
5 W209R Hydrophobic T180 Hydrophilic No No
6 L470P T482 Hydrophobic T482 Hydrophobic No No
7 W312C E340, C342, P316 Hydrophobic E340, C342 Hydrophilic No No
8 A384D Hydrophobic V404 Hydrophilic No No
9 D443N Hydrophilic V404 Hydrophilic No No
10 R44S S13, Y487 Hydrophilic S13, Y487 Hydrophilic No No

Structure-based analysis of SNPs from <xr id="tab:mutations"/>. H-bonds: residues involved in forming hydrogen bonds (cut-off: 3.2 Å). </figtable>