73
Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session I
20-POS
Board 20
The Effects of The Mutations of Arylsulfatase A on Its Structure And Function
Maral Budak
1
, Ayse Eren
2
, Kutlu Ülgen
2
, Elif Özkirimli Ölmez
2
.
1
Boğaziçi University, İstanbul, Turkey,
2
Boğaziçi University, İstanbul, Turkey.
Arylsulfatase A (ASA) is a lysosomal enzyme catalyzing the hydrolysis of sulfate ester bonds.
Its major substrate is cerebroside-3 sulphate and the product of the hydrolysis reaction,
cerebroside, is the major constituent of myelin sheats. In case of the deficiency of this enzyme,
myelin sheath cannot be produced, as a result demyelination of neurons occurs leading to MLD
(Metachromatic leukodystrophy disease). MLD has various lethal neurological symptoms, such
as difficulties in walking and swallowing, spasticity etc. Özkara and coworkers (200x) identified
some MLD patients with mutations E307K, T391S, W318C, N350S on ASA, but almost no ASA
activity.
Our aim is to find the mechanism, which changes the ASA activity and functionality, as a cause
of stated mutations. First, data mining about ASA’s structure and function, activators and MLD
were performed by Ayşe Eren and Maral Budak. Secondly, 3D structure of ASA was
investigated in order to get a better understanding of the sites of the mutations and their closeness
to the active site, and it is found out that they are rather far from there. Next, BLAST and
COBALT were used to investigate whether the interest mutations are on the conserved sites or
not, by comparing ASA with phylogenetical relatives. The free energies of the wild type and
mutated types of ASA have been calculated using FoldX. It is predicted that these mutations
detoriate the enzyme energy and maybe cause another minimum for the enzyme to fold in
another conformation or some emergent intermolecular interactions, caused by the mutated
residues effect enzyme’s proper activity, thus it becomes inactive or cannot dimerize or
octamerize.
