User:Boris Brumshtein: Difference between revisions

Line 94:

#[[2v3d]] ACID-BETA-GLUCOSIDASE WITH N-BUTYL-DEOXYNOJIRIMYCIN

#[[2v3e]] ACID-BETA-GLUCOSIDASE WITH N-NONYL-DEOXYNOJIRIMYCIN

==MY CURRENT RESEARCH==

My PhD research thesis focuses on the enzyme acid-beta-glucosidase, with the

emphasis on the enzyme's structure and its interactions with various ligands and

their pharmacological potential.

The enzyme is involved in a Gaucher disease, which is the most common

lysosomal storage disease, and is associated with mutations in the gene

coding for the enzyme acid-beta-glucosidase.

There are ~200 known mis-sense mutations, which result in substitution of amino acids in the protein.

Some mutations cause complete deactivation of the enzyme; others impair its stability, and some

affect both activity and stability.

There are three known phenotypes of the disease: a mild, severe and acute.

The acute phenotype is neuropathic, while severe and mild symptoms are caused by accumulation of

glucoceramide in macrophage cells resulting in bone atrophy, spleen enlargement, etc.

We have solved structures of recombinant acid-beta-glucosidase expressed in both mammalian

and plant cell cultures, as well as of complexes with molecules, which have been shown to inhibit

glucoceramide synthase and in a less extent acid-beta-glucosidase. Yet these molecules were shown

to stabilize several mutant forms of the mutant enzyme in Gaucher disease.

We have shown that the molecular basis for the stabilization of acid-beta-glucosidase by these small molecules

is by binding to the active site and contributing additional non-covalent bonds that stabilize the enzyme's overall structure.

The page is always under construction ; last update [[User:Boris Brumshtein|Boris Brumshtein]] 14:12, 8 June 2008 (IDT)

[[Image:UnderConstruction.gif| 300px| thumb | left]]

User:Boris Brumshtein: Difference between revisions

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@@ Line 94: / Line 94: @@
 #[[2v3d]] ACID-BETA-GLUCOSIDASE WITH N-BUTYL-DEOXYNOJIRIMYCIN
 #[[2v3e]] ACID-BETA-GLUCOSIDASE WITH N-NONYL-DEOXYNOJIRIMYCIN
+==MY CURRENT RESEARCH==
+My PhD research thesis focuses on the enzyme acid-beta-glucosidase, with the
+emphasis on the enzyme's structure and its interactions with various ligands and
+their pharmacological potential.
+The enzyme is involved in a Gaucher disease, which is the most common
+lysosomal storage disease, and is associated with mutations in the gene
+coding for the enzyme acid-beta-glucosidase.
+There are ~200 known mis-sense mutations, which result in substitution of amino acids in the protein.
+Some mutations cause complete deactivation of the enzyme; others impair its stability, and some
+affect both activity and stability.
+There are three known phenotypes of the disease: a mild, severe and acute.
+The acute phenotype is neuropathic, while severe and mild symptoms are caused by accumulation of
+glucoceramide in macrophage cells resulting in bone atrophy, spleen enlargement, etc.
+We have solved structures of recombinant acid-beta-glucosidase expressed in both mammalian
+and plant cell cultures, as well as of complexes with molecules, which have been shown to inhibit
+glucoceramide synthase and in a less extent acid-beta-glucosidase. Yet these molecules were shown
+to stabilize several mutant forms of the mutant enzyme in Gaucher disease.
+We have shown that the molecular basis for the stabilization of acid-beta-glucosidase by these small molecules
+is by binding to the active site and contributing additional non-covalent bonds that stabilize the enzyme's overall structure.
 The page is always under construction ; last update [[User:Boris Brumshtein|Boris Brumshtein]] 14:12, 8 June 2008 (IDT)
 [[Image:UnderConstruction.gif| 300px| thumb | left]]