Structural Characterization and Determinants of Specificity of Single-Chain Antibody Inhibitors of Membrane-Type Serine Protease 1
Abstract
Membrane-type serine protease 1 (MT-SP1) is a cancer-associated serine protease implicated in the tumorogenesis and metastasis of breast cancer. Inhibition of MT-SP1 activity has been shown to decrease metastatic potential. We have developed a number of potent and specific single-chain (scFv) antibody inhibitors to MT-SP1, and have begun to characterize their mechanism of inhibition. Through kinetic characterization and site-directed mutagenesis experiments, it has been determined that three potent inhibitors have separate and novel mechanisms of inhibition which do not mimic either biologically or pharmaceutically relevant protease inhibitors. These novel modes of binding and inhibition are the basis for their specificity, and suggest these inhibitors will have less cross-reactivity and toxicity problems when used in vivo to further dissect the role of MT-SP1 in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2008
- Accession Number
- ADA487918
Entities
People
- Christopher J. Farady
Organizations
- University of California, San Francisco