H. sapiens Caspase-3
Alex Seaver '17 and Coire Gavin-Hanner '18
Contents:
I. Introduction
Model View:
Color Scheme:
Cysteine Asp-specific Proteases (CASPASEs) are enzymes that play
important roles in Apoptosis and inflammation. The Caspases identified
thus far can be organized into three groups: Inflammation Caspases (1,
4, 5, 11, and 12), Initiator Caspases (2, 8, 9, 10), and Executioner
Caspases (3, 6, and 7). Caspase-3 is a key executioner enzyme that, in
addition to Caspase-7, is necessary for apoptosis and normal mammalian
life.
In healthy cells, Caspases exist as inactive procaspase composed of a
Large subunit (p20), a small subunit (p10), and a prodomain of varying
length. Once activated, the prodomains form a heterodimer with two
subunits. Two heterodimers form a heterotetramer in a mature Caspase.
Caspases may play a role in many diseases such as Alzheimer's. Their
implication in such diseases makes them very attractive targets for
drugs.
II. Procaspase and Activation
In healthy cells Caspase-3 exists as Procaspase-3, a
homodimer made up of 17 kDa and 12 kDa subunits. There are two
pathways that activate Procaspase-3, the extrinsic and intrinsic.
The extrinsic pathway is activated by a TNFR1-binding substrate, a
signal from outside of the cell to begin apoptosis. This pathway
activates Caspase-8, an initiator Caspase which can cleave the
Procaspase-3 homodimer. The intrinsic pathway is activated from
within the cell itself as a self-recognition of damage. The
intrinsic pathway activates Caspase-9, an initiator Capsase similar
to Caspase-8.
III. General Structure
The mature Caspase is a
homodimer of heterodimers, each formed from the
and
subunits of the procaspase. At their core, each heterodimer has
six
surrounded by five
.
The heterodimers are held together mostly by hydrophobic
interactions. Some electrostatic interactions are also present.
IV. Active Site
The active site is made up of four loops. Loops
and 4
bind with the substrate and provide selectivity.
V. Binding and Catalytic Activity
VI. References
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