Molecular Playground/Caspase-7 Dynamics

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.

Caspase-7 as studied in the Hardy Lab Caspase-7 as studied in the Hardy Lab

spinqualitylabelsall models Conformational Dynamics between active and allosterically inhibited caspase-7 elucidate the mechanism of allostery in this important class of cysteine proteases. Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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-7Forms 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-7Molecular 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.

(Expand CBI Entry for Caspases (click to edit) )(Expand CBI Entry for Caspases (click to edit) )

(Expand CBI Entry for Caspases (click to edit) )