Fabry:Homology based structure predictions
Fabry Disease » Homology based structure predictions
The following analyses were performed on the basis of the α-Galactosidase A sequence. Please consult the journal for the commands used to generate the results.
Contents
Dataset preparation
<figtable id="tab:datasetHHpred"> Dataset HHpred
| pdb ID | E-value | Identity in % |
|---|---|---|
| > 80% sequence identity | ||
| 3hg3 | 8.6e-90 | 100 |
| 40% - 80% sequence identity | ||
| 1ktb | 4.2e-85 | 53 |
| < 30% sequence identity | ||
| 3cc1 | 5.5e-74 | 25 |
| 1zy9 | 3.1e-48 | 13 |
| 3a24 | 7.8e-40 | 17 |
| 2xn2 | 5.3e-37 | 15 |
| 2d73 | 5.7e-36 | 14 |
| 3mi6 | 1.4e-31 | 15 |
| 2yfo | 9.1e-30 | 13 |
| 2f2h | 2.7e-20 | 17 |
| 2g3m | 2.2e-20 | 16 |
| 3nsx | 6e-20 | 13 |
| 3lpp | 2.2e-18 | 15 |
| 3l4y | 1.9e-18 | 15 |
| 3top | 3.6e-18 | 12 |
| 2xvl | 3.2e-18 | 16 |
| 2x2h | 4.9e-16 | 13 |
</figtable>
<figtable id="tab:datasetCOMA"> Dataset COMA
| pdb ID | E-value | Identity in % |
|---|---|---|
| > 80% sequence identity | ||
| - | - | - |
| 40% - 80% sequence identity | ||
| 1ktb | 1.7e-61 | 52 |
| < 30% sequence identity | ||
| 3lrk | 1.2e-66 | 23 |
| 3a21 | 2.7e-65 | 26 |
| 1szn | 3.7e-59 | 22 |
| 3cc1 | 5.2e-58 | 19 |
| 1zy9 | 1.7e-39 | 9 |
| 3mi6 | 4.3e-38 | 11 |
| 2yfn | 4.4e-35 | 10 |
| 2d73 | 1.9e-32 | 9 |
| 3a24 | 5.6e-30 | 10 |
| 1xsi | 1.9e-12 | 10 |
| 2g3m | 2.4e-11 | 10 |
| 3pha | 2.9e-10 | 6 |
| 3lpo | 4.7e-09 | 8 |
| 2x2h | 8.2e-09 | 8 |
| 3mo4 | 1.2e-08 | 7 |
| 2xvg | 2.4e-08 | 8 |
| 3ton | 4.3e-08 | 8 |
| 2xib | 1e-07 | 7 |
| 3eyp | 1.6e-06 | 8 |
| 3k1d | 3.5e-06 | 9 |
| 2zwy | 8.8e-06 | 9 |
| 3gza | 1.8e-05 | 8 |
| 3m07 | 2.3e-05 | 7 |
| 1eh9 | 0.00013 | 6 |
| 1gvi | 0.00035 | 8 |
| 1aqh | 0.00039 | 5 |
| 1mwo | 0.00058 | 7 |
| 3vmn | 0.0018 | 9 |
| 1bf2 | 0.0019 | 6 |
| 3aml | 0.0019 | 8 |
</figtable>
We performed a HHpred as well as a COMA search, to generate three distinct datasets. Since COMA did not find any homologue structures with a similarity above 41% (see <xr id="tab:datasetCOMA"/>), we used the dataset created with the HHpred search and the script described in the journal. Hereby we found one structure with a similarity above 80%, one with a similarity between 40 and 80% and 15 with sequence similarity below 30%, of which 14 had a similarity of under 20% (see <xr id="tab:datasetHHpred" />). All HHpred matches had an E-value below 1e-15, for the COMA homologues we tried a less strict threshold of 0.002.
In most of the cases we used the structures 3hg3, 1ktb and 3cc1 for modelling, because either they are the only representatives in their class, or in the case od 3cc1, the sequence identity did not seem too low.
In this case it is important to mention, that although the identity of 3hg3 is 100%, it is not the pdb structure annotated for the AGAL protein, but the structure of the substrate bound catalytic mechanism, hence the high similarity.
1ktb is the X-ray structure for the already mentioned α-N-acetylgalactosiminidase in chicken, which in future might be used for enzyme replacement therapy in the treatment of Fabry Disease.
The last one of the frequently used structures, 3cc1, is the x-ray structure of a putative α-N-acetylgalactosiminidase in in Bacillus Halodurans.
