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|Title:||Mapping of human plasma kallikrein active site by design of peptides based on modifications of a Kazal-type inhibitor reactive site|
|Authors:||Nunes, Viviane Abreu [UNIFESP]|
Gozzo, Andrezza Justino [UNIFESP]
Sampaio, Misako Uemura [UNIFESP]
Juliano, Maria Aparecida [UNIFESP]
Sampaio, Claudio Augusto Machado [UNIFESP]
Araujo, Mariana da Silva [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
|Publisher:||Kluwer Academic/plenum Publ|
|Citation:||Journal of Protein Chemistry. New York: Kluwer Academic/plenum Publ, v. 22, n. 6, p. 533-541, 2003.|
|Abstract:||Human plasma kallikrein (huPK) is a proteinase that participates in several biological processes. Although various inhibitors control its activity, members of the Kazal family have not been identified as huPK inhibitors. in order to map the enzyme active site, we synthesized peptides based on the reactive site (PRILSPV) of a natural Kazal-type inhibitor found in Cayman plasma, which is not an huPK inhibitor. As expected, the leader peptide (Abz-SAPRILSPVQ-EDDnp) was not cleaved by huPK. Modifications to the leader peptide at P-1', P-3' and P-4' positions were made according to the sequence of a phage display-generated recombinant Kazal inhibitor (PYTLKWV) that presented huPK-binding ability. Novel peptides were identified as substrates for huPK and related enzymes. Both porcine pancreatic and human plasma kallikreins cleaved peptides at Arg or Lys bonds, whereas human pancreatic kallikrein cleaved bonds involving Arg or a pair of hydrophobic amino acid residues. Peptide hydrolysis by pancreatic kallikrein was not significantly altered by amino acid replacements. the peptide Abz-SAPRILSWVQ-EDDnp was the best substrate and a competitive inhibitor for huPK, indicating that Trp residue at the P-4' position is important for enzyme action.|
|Appears in Collections:||Artigo|
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