2a8i: Difference between revisions

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==Overview==

Taspase1 catalyzes the proteolytic processing of the mixed lineage, leukemia (MLL) nuclear protein, which is required for maintaining Hox gene, expression patterns. Chromosomal translocations of the MLL gene are, associated with leukemia in infants. Taspase1, a threonine aspartase, is a, member of the type 2 asparaginase family, but is the only protease in this, family. We report here the crystal structures of human activated Taspase1, and its proenzyme, as well as the characterization of the effects of, mutations in the active site region using a newly developed fluorogenic, assay. The structure of Taspase1 has significant differences from other, asparaginases, especially near the active site. Mutation of the catalytic, nucleophile, Thr234, abolishes autocatalytic processing in cis but does, not completely block proteolysis in trans. The structure unexpectedly, showed the binding of a chloride ion in the active site, and our kinetic, studies confirm that chlorides ions are inhibitors of this enzyme at, physiologically relevant concentrations.

Taspase1 catalyzes the proteolytic processing of the mixed lineage leukemia (MLL) nuclear protein, which is required for maintaining Hox gene expression patterns. Chromosomal translocations of the MLL gene are associated with leukemia in infants. Taspase1, a threonine aspartase, is a member of the type 2 asparaginase family, but is the only protease in this family. We report here the crystal structures of human activated Taspase1 and its proenzyme, as well as the characterization of the effects of mutations in the active site region using a newly developed fluorogenic assay. The structure of Taspase1 has significant differences from other asparaginases, especially near the active site. Mutation of the catalytic nucleophile, Thr234, abolishes autocatalytic processing in cis but does not completely block proteolysis in trans. The structure unexpectedly showed the binding of a chloride ion in the active site, and our kinetic studies confirm that chlorides ions are inhibitors of this enzyme at physiologically relevant concentrations.

==About this Structure==

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[[Category: Homo sapiens]]

[[Category: Single protein]]

[[Category: Dunn, B.M.]]

[[Category: Dunn, B M.]]

[[Category: Khan, J.A.]]

[[Category: Khan, J A.]]

[[Category: Tong, L.]]

[[Category: asparaginase ]]

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[[Category: threonine aspartase]]

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@@ Line 4: / Line 4: @@
 ==Overview==
-Taspase1 catalyzes the proteolytic processing of the mixed lineage, leukemia (MLL) nuclear protein, which is required for maintaining Hox gene, expression patterns. Chromosomal translocations of the MLL gene are, associated with leukemia in infants. Taspase1, a threonine aspartase, is a, member of the type 2 asparaginase family, but is the only protease in this, family. We report here the crystal structures of human activated Taspase1, and its proenzyme, as well as the characterization of the effects of, mutations in the active site region using a newly developed fluorogenic, assay. The structure of Taspase1 has significant differences from other, asparaginases, especially near the active site. Mutation of the catalytic, nucleophile, Thr234, abolishes autocatalytic processing in cis but does, not completely block proteolysis in trans. The structure unexpectedly, showed the binding of a chloride ion in the active site, and our kinetic, studies confirm that chlorides ions are inhibitors of this enzyme at, physiologically relevant concentrations.
+Taspase1 catalyzes the proteolytic processing of the mixed lineage leukemia (MLL) nuclear protein, which is required for maintaining Hox gene expression patterns. Chromosomal translocations of the MLL gene are associated with leukemia in infants. Taspase1, a threonine aspartase, is a member of the type 2 asparaginase family, but is the only protease in this family. We report here the crystal structures of human activated Taspase1 and its proenzyme, as well as the characterization of the effects of mutations in the active site region using a newly developed fluorogenic assay. The structure of Taspase1 has significant differences from other asparaginases, especially near the active site. Mutation of the catalytic nucleophile, Thr234, abolishes autocatalytic processing in cis but does not completely block proteolysis in trans. The structure unexpectedly showed the binding of a chloride ion in the active site, and our kinetic studies confirm that chlorides ions are inhibitors of this enzyme at physiologically relevant concentrations.
 ==About this Structure==
@@ Line 13: / Line 13: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Dunn, B.M.]]
+[[Category: Dunn, B M.]]
-[[Category: Khan, J.A.]]
+[[Category: Khan, J A.]]
 [[Category: Tong, L.]]
 [[Category: asparaginase ]]
@@ Line 22: / Line 22: @@
 [[Category: threonine aspartase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:14:03 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:24:38 2008''