Talk:Tay-Sachs Disease 2012

From Bioinformatikpedia


The text is well organized, with comprehensive information about the disease. Scientific terms are used appropriately and the content is comprehensible. In general, using short sentences instead of subordinate clauses would make the text even better to understand. All topics are cited extensively which allows the reader to easily retrieve further information.


  • For table 1 in section "Distinction to other sphingolipidoses ", the explanation to the columns could be in a separate paragraph. Adding visible table border might look better (get help here [1]).
Thanks, we adjusted the table and added some highlights to the caption which should make things easier to read
  • Using 'Biochemical basis' instead of 'Biochemical Basis' would make the captions more consistent.
Indeed! fixed
  • You might make 'Distinction to other sphingolipidoses' a subtopic of 'Biochemical basis' to reduce the number of main topics (currently 11).
We decided against it for now, but you are right that we have quite a few sections. Maybe we will merge prevalence and/or genetic basis into some of the other sections


  • 1 Summary: Here it is not clear that GM2 is the substrate that can not be degraded.
  • Adding an image of the "Cherry-red" or some pictures of the symptoms might give the readers an intuitive impression of the disease.
Agreed, some will be added tomorrow
  • In section "Prevalence ", maybe add some statistic about the disease frequency of the Ashkenazi Jews and eastern Quebec French Canadians population.
We will try to find something. For now all we know is that the screening programs greatly reduced the numbers, but there ought to be information on what those numbers are. We're at it.
  • In section "Distinction to other sphingolipidoses", a short explanation of "sphingolipidoses" might be helpful.
Added a short intro to the section, explaining this.
  • 5.2 Catalytic activity: It is hard to understand why the inhibitor provides information about potential residues that bind the true substrate GM2. Your pymol picture looks quite nice, but it is not obvious why you are highlighting the inhibitor instead of GM2. Your reference to the original publication is of course helpful.
Yes we will try to make this clearer in the text. To our knowledge there is currently no crystal structure of Hex A with the native substrate GM2 bound, available. This might be due to the comparably large size of GM2. In the publication they did a docking experiment based on this structure by removing NGT and trying to dock GM2 into the pocket. This is of course sub-optimal since the docking algorithm might not have found the native conformation. Nonetheless we agree that it would be interesting to look at, however we are not sure if this data is available. Furthermore you are right that the residues important for binding NGT do not necessarily play any role for GM2. We showed the figure nonetheless since the paper shows that the binding mechanism somewhat mimics that of GM2 (actually NGT acts as a molecular chaperone and stabilizes Hex A, allowing proper folding for some mutant alleles) and therefore seems to be as close as we can get with the current data.
I actually looked at the PDB again and there seem to be crystal structures from Hexosaminidase with bound GlcNac (e.g. 1m01) which would be closer to having a GM2 bound. We will take a look at how these bacterial proteins are comparable to the human one and if the GlcNac is bound in the alpha subunit's active site. (A bound GalNac would be even better, however these structures seem to be limited to beta/beta homodimers, which are not helpful for us)
  • 7 Mutations: Listing all mutations is actually not necessary.
You are right. Since it also takes up quite some space and decreases readability we moved it to a separate site for now. We will see how the practical develops in terms of handling mutations.

Best regards,
Christof, Guokun