3ncl
Crystal Structure of MT-SP1 bound to Benzamidine Phosphonate InhibitorCrystal Structure of MT-SP1 bound to Benzamidine Phosphonate Inhibitor
Structural highlights
DiseaseST14_HUMAN Defects in ST14 are a cause of ichthyosis autosomal recessive with hypotrichosis (ARIH) [MIM:610765. ARIH is a skin disorder characterized by congenital ichthyosis associated with the presence of less than the normal amount of hair.[1] FunctionST14_HUMAN Degrades extracellular matrix. Proposed to play a role in breast cancer invasion and metastasis. Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site. Publication Abstract from PubMedThe ability to follow enzyme activity in a cellular context represents a challenging technological frontier that impacts fields ranging from disease pathogenesis to epigenetics. Activity-based probes (ABPs) label the active form of an enzyme via covalent modification of catalytic residues. Here we present an analysis of parameters influencing potency of peptide phosphonate ABPs for trypsin-fold S1A proteases, an abundant and important class of enzymes with similar substrate specificities. We find that peptide length and stability influence potency more than sequence composition and present structural evidence that steric interactions at the prime-side of the substrate-binding cleft affect potency in a protease-dependent manner. We introduce guidelines for the design of peptide phosphonate ABPs and demonstrate their utility in a live-cell labeling application that specifically targets active S1A proteases at the cell surface of cancer cells. Peptide length and leaving-group sterics influence potency of Peptide phosphonate protease inhibitors.,Brown CM, Ray M, Eroy-Reveles AA, Egea P, Tajon C, Craik CS Chem Biol. 2011 Jan 28;18(1):48-57. PMID:21276938[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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