University of Massachusetts
Department of Chemistry
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 © 2007
University of Massachusetts Amherst




Caspases are a family of cysteine aspartate proteases that regulate cell death (apoptosis) and inflammation. Their central role in these processes makes them attractive drug targets for treating cancer, stroke, heart attack, arthritis and Alzheimer's disease. In fact, it is estimated that up to 50% of diseases for which there is no suitable cure are the result of irrgularities in apoptosis. We use a variety of tools including x-ray crystallography, biochemistry, and protein design to probe the function of capases.

Caspase Regulation

During the past decade a number of structures of caspases in the pro-caspase zymogen, cleaved caspase, active site bound and allosterically inhibited forms have been determined by x-ray crystallography. Nevertheless, the detailed mechanism of caspase activation remains hazy. Different caspases have alternate mechanisms of both activation and inhibition. We design and use caspase activators, inhibitors and effectors to control and investigate caspase activity.

Discovery and Control of a Caspase Allosteric Site



Allosteric Site Identification

Allosteric sites were once thought to be rare, evolutionarily conserved entities. As structure determination accompanies high-throughput drug discovery, we see that allosteric sites are less rare than we once believed. Small molecules have a propensity for finding new allosteric sites which occur all over protein surfaces. PTP1B and Factor VIIa are two examples of protein where multiple allosteric sites have been discovered. We are involved in discovering and exploiting new allosteric sites.

Serendipitous Allosteric Sites Review



Protein Design

Design Script
The ultimate frontier for the protein chemist is the ability to design and control protein function. We apply recent advances from the protein design field to make new versions of important proteins that are regulated by the drug molecule we choose. Most recently we have designed a caspase activatable GFP.


Lab Updates

Samantha Nicholls successfully defends her dissertation.

Elih Velazquez publishes caspase-6 zinc structure in JBC.

Elih Velazquez successfully defends his dissertation.










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