Structure-based mutation analysis TSD

No citations, I don't read THAT many books :P

The journal of this task can be found here here.

Mutations

As the week before only disease causing SNPs were assigned to us some mutations had to be replaced. Additionally the reference pdb stricture limited the possibilities as only the second domain was retained fpr the following analzsis. Thus a almost new set of SNPs was chosen:

R178H, R178C, P183L, D207E, S293I, F434L, L451V, E482K, L484Q, E506D

Structure preparation

There are two structures resolved for the HEXA_HUMAN reference sequence used for the course of this practical. The struture of this Uniprot entry is found in the alpha-chains of the PDB-IDs and 2gjx and 2gk1 both form the same publication <ref name="hexa_pdb_ref">Lemieux, M., Mark, B., & Cherney, M. (2006). Crystallographic Structure of Human beta-Hexosaminidase A: Interpretation of Tay-Sachs Mutations and Loss of GM2 Ganglioside Hydrolysis. Journal of molecular biology, 359(4), 913-29. doi:10.1016/j.jmb.2006.04.004</ref>. Unfortunately a xx residue stretch towards the N-terminus of the protein (residues x to y) is unresolved in both structures. However as previously shown the alpha subunit of Hex A consists of two domains. The N-terminal domain, Glyco_hydro_20b, is not involved in catalysis. Therefore, to evade problems with the missing backbone in the course of this task, the structure was truncated to contain only the C-terminal, catalytic domain, Glyco_hydro_20. In concordance with previous tasks '2gjx was chosen as the reference structure. Details on the alteration of the structure according to the measures described above can be found in the journal.