The first allelic variant from for aspartoacylase (ASPA) in omim is an 854 A-C transversion. A transversion is the substitution of a purine for a pyrimidine. This causes a glutamic acid to alanine switch at the 285 spot. Alanine is one of the simplest AAs with a functional group composed of only a methyl. The methyl on alanine is non reactive so you will almost never see alanine directly involved in protein function. Glutamic Acid on the other hand is highly reactive and found in many protein functions. So what is happening is the replacement of a highly reactive AA with an essentially non reactive AA.
The substitution at 285 is predicted to be part of the catalytic domain of ASPA. This mutations was found in 18 Ashkenazi Jew patients with Canavan disease. Of 879 Ashkenazi Jew scanned in the Elpeleg et all (1994) study 1 in 59 were found to be heterozygote carriers. This study showes the importance for Ashkenazi Jews to scan for this mutation.
Below is the reaction that ASPA takes part in which will play an important role when discovering how the structural changes, of the E to A substitution, affects this enzyme.
ASPA is a hydrolase enzyme whose reaction looks like this: N-acyl-L-aspartate + H2O 
a carboxylate + L-aspartate
Using Protean 3D the first thing you will notice is that according to the Chou-Fasman secondary structure analysis the E285A variant appears to have a higher likely hood of a beta region at 285. Which when it comes to protein interactions the shape of the protein is very important. So having structural changes at what is believe to be the catalytic domain will mostly likely result in less or different binding.
Another change and what I believe to be the most significant is the change to the hydrophobicity. According to both Kyte-Doolittle and Hopp-Woods the E285 variant becomes more hydrophobic. So with ASPA being a hydrolase enzyme and relying on water for its catalytic affect making the catalytic domain more hydrophibic is going to play a substantial role in how well ASPA is able to catalyze its reaction. Protean also shows the ASPA E285A variant to be more hydrophobic. Also according to Yasanandana S. Wijayasinghe et all
“The structure of the E285A mutant, the most common clinical mutant, reveals that the loss of hydrogen bonding interactions with the carboxylate side chain of Glu285 disturbs the active site architecture, leading to altered substrate binding and lower catalytic activity.”
The last difference between ASPA and ASPA E285A according to Lehninger charge density plot is the negative region. Which is obviously due in part to the difference between Glu and Ala. Glu has a carboxylic acid functional group while Ala has a methyl group. Obviously the carboxylic acid group is going to be much more negatively charged. This is going to play into the hyphobicity difference we saw above.
A few things didn’t change with the substitution. The antigenicity according to the Jameson-Wolf plot did not change. This makes sense because the structural change was to such a small area of the protein. Also the flexibility remained the same. This I believe is another case of the change being so small but to such an important area.
Over all the E285A variant is such a small change when not looking at the 3D structure. It is only a single AA change in a protein that is 314 AAs long. But that change unluckily falls on the catalytic domain and turns ASPA into a much more hydrophobic enzyme unable to catalyze to its full potential.
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