Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

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.

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