Fabry:Structure-based mutation analysis

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