title: Caspase-1 recognizes extended cleavage sites in its natural substrates.
abstract: OBJECTIVE
  The preferred amino acids in the proteolytic sites have been considered to be similar between caspase-1 and caspase-9, which do not support their differential functions in inflammatory pyroptosis and apoptosis. We attempted to solve this problem.
  
  
  METHODS
  We analyzed the flanking 20 amino acid residues in the cleavage sites in 34 caspase-1 and 11 capase-9 experimentally identified substrates.
  
  
  RESULTS
  This study has made the following findings: first, we verified that caspase-1 and caspase-9 shared 100% aspartic acid in the P1 position. However, the structures in the cleavage sites of most caspase-1 substrates are different from that of caspase-9 substrates in the following three aspects, (a) the amino acid residues with the statistically high frequencies; (b) the hydrophobic amino acid occurrence frequencies; and (c) the charged amino acid occurrence frequencies; second, the amino acid pairs P1-P1' are different; third, our identified cleavage site patterns are useful in the prediction for the 91.4% cleavage sites of 35 new caspase-1 substrates.
  
  
  CONCLUSIONS
  Since most caspase-1 substrates are involved in vascular function, inflammation and atherogenesis, our novel structural patterns for the caspases' substrates are significant in developing new diagnostics and therapeutics.
authors.affiliation: Department of Pharmacology, Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, United States.
authors.forename: Jerry
authors.initials: J
authors.lastname: Shen
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.forename: Jietang
authors.initials: J
authors.lastname: Mai
authors.forename: Xinyu
authors.initials: X
authors.lastname: Xiong
authors.forename: Meghana
authors.initials: M
authors.lastname: Pansuria
authors.forename: Jingshan
authors.initials: J
authors.lastname: Liu
authors.forename: Erin
authors.initials: E
authors.lastname: Maley
authors.forename: Najam Us
authors.initials: NU
authors.lastname: Saqib
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yang
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D017209:Apoptosis; D001665:Binding Sites; D020170:Caspase 1 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation; D008954:Models, Biological; D011485:Protein Binding; D013379:Substrate Specificity
chemical_list: D000596:Amino Acids; D053453:Caspase 9; D020169:Caspases; D020170:Caspase 1