Molecular Playground/Caspase-7 Dynamics

From Proteopedia

Jump to: navigation, search

Caspases are a family of CBI Molecules being studied in the University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground.

Contents

Caspase-7 as studied in the Hardy Lab

Conformational Dynamics between active and allosterically inhibited caspase-7 elucidate the mechanism of allostery in this important class of cysteine proteases.

Conformational dynamics in Caspase-7 are mediated by an 'Allosteric Toggle' mechanism in which binding of allosteric inhibitor DICA to CYS 290 pushes TYR 223 into 'up' conformation forcing ARG 187 'out' into a form that is physically incompatible with substrate binding.

The cleaved termini of the large and small subunits which form the active site loop bundle become highly ordered in active conformation, and highly disordered in allosterically inhibited form (so much so that they cannot be resolved crystallographically).

Forms of Caspase-7

  • , trapping protein in active/substrate bound conformation.
  • trapping protein in a form incompatible with substrate binding.
  • of Caspase-7.

Molecular Playground banner for Caspase-7

Molecular Playground banner: Conformational Dynamics between active and allosterically inhibited caspase-7 elucidate the mechanism of allostery in this important class of cysteine proteases.

3D structures of caspase

Caspase

Additional Resources

For additional information, see: Cancer

Proteopedia Page Contributors and Editors (what is this?)

Daniel Seeman, Michal Harel, Maureen E. Hill, David Canner

Personal tools