The mechanism of inhibition of antibody-based inhibitors of membrane-type serine protease 1 (MT-SP1).


The mechanisms of inhibition of two novel scFv antibody inhibitors of the serine protease MT-SP1/matriptase reveal the basis of their potency and specificity. Kinetic experiments characterize the inhibitors as extremely potent inhibitors with K(I) values in the low picomolar range that compete with substrate binding in the S1 site. Alanine scanning of the loops surrounding the protease active site provides a rationale for inhibitor specificity. Each antibody binds to a number of residues flanking the active site, forming a unique three-dimensional binding epitope. Interestingly, one inhibitor binds in the active site cleft in a substrate-like manner, can be processed by MT-SP1 at low pH, and is a standard mechanism inhibitor of the protease. The mechanisms of inhibition provide a rationale for the effectiveness of these inhibitors, and suggest that the development of specific antibody-based inhibitors against individual members of closely related enzyme families is feasible, and an effective way to develop tools to tease apart complex biological processes.

Submission Details


Submitter: Shu-Ching Ou

Submission Date: Feb. 27, 2019, 3:18 p.m.

Version: 1

Publication Details
Farady CJ;Sun J;Darragh MR;Miller SM;Craik CS,J Mol Biol (2007) The mechanism of inhibition of antibody-based inhibitors of membrane-type serine protease 1 (MT-SP1). PMID:17475279
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
99.6 Suppressor of tumorigenicity 14 protein Q9Y5Y6 ST14_HUMAN