Protein substrates with small hydrophobic P1 residues

Protein substrates with small hydrophobic P1 residues is a classification used to describe the specificity of certain proteases rather than a single molecular target. In the Schechter and Berger nomenclature, the P1 residue is the amino acid on the amino-terminal side of the peptide bond that is cleaved (Schechter & Berger, 1967). Proteases such as neutrophil elastase and pancreatic elastase specifically recognize and cleave peptide bonds where the P1 position is occupied by small hydrophobic residues like alanine or valine (Bieth, 1986). These substrates include structural proteins like elastin and various signaling molecules involved in the inflammatory response. Because this term encompasses a wide variety of proteins sharing a common cleavage motif, it does not represent a discrete therapeutic target for drug development. Instead, therapeutic interventions are directed at the enzymes (e.g., elastases) that act upon these substrates to prevent excessive tissue degradation in diseases such as COPD and cystic fibrosis (Rawlings et al., 2018).

Other names

Elastase-like substratesP1 small hydrophobic substratesElastase cleavage motifsCHEMBL2366505

Not applicable; this is a substrate specificity profile, not a drug target.