Yeda Research and Develpment & Co. Ltd

Israel Silman

Joel L Sussman

Dan S Tawfik

Leonid Gaydukov

Amir Aharoni

Anthony Futerman

Lilly Toker

Michal Harel

Hay Dvir

Isolated polynucleotides and polypeptides encoded therefrom are provided. These include mutated PON enzymes with increased, modified or substantially the same substrate specificity as compared to respective wild-type PON. Also provided are kits and methods using these enzymes.

PON polypeptides, polynucleotides encoding same and compositions and methods utilizing same

A method of identifying a compound capable of correcting an impaired enzymatic activity of a mutant glucocerebrosidase molecule, the method comprising: (a) obtaining a first set of structure coordinates, the first set of structure coordinates defining a 3D structure of a glucocerebrosidase molecule capable of displaying normal enzymatic activity or a portion thereof; (b) computationally generating using the first set of structure coordinates a second set of structure coordinates, the second set of structure coordinates defining a predicted 3D structure of the mutant glucocerebrosidase molecule or a portion thereof; and (c) computationally identifying, using the second set of structure coordinates, a compound capable of interacting with the mutant glucocerebrosidase molecule in such a way as to correct the impaired enzymatic activity thereof, thereby identifying the compound capable of correcting the impaired enzymatic activity of the mutant glucocerebrosidase molecule. A glucocerebrosidase preparation comprising a population of glucocerebrosidase molecules, wherein substantially each of said glucocerebrosidase molecules: (i) has an amino acid sequence at least 95 percent homologous to an amino acid sequence set forth by SEQ ID NO: 1 or 8; (ii) is glycosylated at, or has an aspartatic acid residue at, glycosylation residue 1 of said amino acid sequence; and (iii) is independently unglycosylated at one or more glycosylation residues selected from the group consisting of glycosylation residues 2, 3 and 4 of said amino acid sequence.

Partially deglycosylated glucocerebrosidase polypeptide and crystals thereof

Pon polypeptides polynucleotides encoding same and compositions and methods utilizing same

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Rehovot, Israel

Israel Silman