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PDBsum entry 4dcp
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Hydrolase/hydrolase inhibitor
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PDB id
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4dcp
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References listed in PDB file
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Key reference
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Title
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Molecular insight into the role of the leucine residue on the l2 loop in the catalytic activity of caspases 3 and 7.
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Authors
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H.J.Kang,
Y.M.Lee,
M.S.Jeong,
M.Kim,
K.H.Bae,
S.J.Kim,
S.J.Chung.
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Ref.
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Biosci Rep, 2012,
32,
305-313.
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PubMed id
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Abstract
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Various apoptotic signals can activate caspases 3 and 7 by triggering the L2
loop cleavage of their proenzymes. These two enzymes have highly similar
structures and functions, and serve as apoptotic executioners. The structures of
caspase 7 and procaspase 7 differ significantly in the conformation of the loops
constituting the active site, indicating that the enzyme undergoes a large
structural change during activation. To define the role of the leucine residue
on the L2 loop, which shows the largest movement during enzyme activation but
has not yet been studied, Leu168 of caspase 3 and Leu191 of caspase 7 were
mutated. Kinetic analysis indicated that the mutation of the leucine residues
sometimes improved the Km but also greatly decreased the kcat, resulting in an
overall decrease in enzyme activity. The tryptophan fluorescence change at
excitation/emission = 280/350 nm upon L2-L2' loop cleavage was found to be
higher in catalytically active mutants, including the corresponding wild-type
caspase, than in the inactive mutants. The crystal structures of the caspase 3
mutants were solved and compared with that of wild-type. Significant alterations
in the conformations of the L1 and L4 loops were found. These results indicate
that the leucine residue on the L2 loop has an important role in maintaining the
catalytic activity of caspases 3 and 7.
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