Cloning of the cDNA for the serine protease homolog CAP37/azurocidin, a microbicidal and chemotactic protein from human granulocytes.

Abstract

Human cationic antimicrobial protein (CAP37) is a neutrophil granule protein with monocyte chemotactic and antibacterial activity. A CAP37 cDNA clone of 899 bp was isolated from an HL-60 cDNA library using degenerate oligonucleotide probes based on partial N-terminal sequence of the CAP37 protein. The cDNA sequence predicts an open reading frame of 753 bp encoding a protein of 251 amino acids. A 26-residue eukaryotic signal peptide and a potential 7 amino acid pro-peptide are present at the N-terminus of the protein. The cDNA sequence also predicts three N-linked glycosylation attachment sites and eight intramolecular cysteines. The deduced amino acid sequence of CAP37 shows 44, 42, and 32% homology at the amino acid level to neutrophil elastase, myeloblastin, and cathepsin G, respectively, suggesting that CAP37 is a member of the serine protease gene family. CAP37 does not possess serine protease activity probably due to mutations in two of three residues in the catalytic triad of the "charge relay system." Whereas CAP37 is expressed in undifferentiated HL-60 cells no message is detected in mature neutrophils.

Proteomic adaptations in the kidney reveal orchestration of local and secreted antimicrobial peptides in human pyelonephritis

“…We have found elevated levels of azurocidin-1, also known as cationic antimicrobial protein 37 (CAP37) or heparin-binding protein (HBP) in the kidney and urine of PN patients. Together with cathepsin G and neutrophil elastase, azurocidin-1 is a member of the serine protease family found in the specialized azurophilic granules of neutrophils [35, 36]. Crystallographic analysis indicates that the antibacterial activity of azurocidin-1 is likely mediated by a hydrophobic pocket (residues 20 to 44) that binds to the lipid A of Gram-negative bacteria [37].…”

Effect of Cationic Antimicrobial Protein CAP37 on Cytokine Profile during Corneal Wound Healing

“…CAP37 also binds and neutralizes an outer membrane component of Gram-negative bacteria known as lipopolysaccharide (LPS) [1,4]. In addition to being a pro-inflammatory protein with chemotactic activity towards monocytes/macrophages, and microglia [3,[5][6][7], CAP37 also promotes migration, proliferation, and adhesion of human corneal epithelial cells [8]. In vivo, CAP37 promotes faster corneal re-epithelialization in mouse [9].…”

Chymotrypsin both directly modulates bacterial growth and asserts ampicillin degradation-mediated protective effect on bacteria

“…Another novel serine protease produced by Sarcophaga peregrina showed antibacterial activity against several bacteria (Tsuji et al 1998). The serine protease homolog protein with antibacterial activity was identified from human granulocytes (Morgan et al 1991). The antibacterial activities of these agents are generally broad in target spectrum, but the mechanisms have not been completely elucidated.…”