Azurocidin 1 Explained

Azurocidin also known as cationic antimicrobial protein CAP37 or heparin-binding protein (HBP) is a protein that in humans is encoded by the AZU1 gene.^{[1] [2]}

Function

Azurophil granules, specialized lysosomes of the neutrophil, contain at least 10 proteins implicated in the killing of microorganisms. The protein encoded by this gene is an azurophil granule antimicrobial protein, with monocyte chemotactic and antibacterial activity. It is also an important multifunctional inflammatory mediator.^[3] The genes encoding this protein, neutrophil elastase 2, and proteinase 3 are in a cluster located at chromosome 19pter. All 3 genes are expressed coordinately and their protein products are packaged together into azurophil granules during neutrophil differentiation.

Structure

This encoded protein is a member of the PA clan of proteases but it is not a serine proteinase, because the active site serine and histidine residues are replaced, making it a pseudoenzyme.^[4]

Clinical significance

In patients with fever, high plasma levels of HBP indicates that the patient is at high risk of developing sepsis with circulatory collapse.^[5]

Further reading

• Book: Morgan JG, Pereira HA, Sukiennicki T . Human Neutrophil Granule Cationic Protein CAP37 is a Specific Macrophage Chemotaxin that Shares Homology with Inflammatory Proteinases . Chemotactic Cytokines . 305 . 89–96 . 1992 . 1755383 . 10.1007/978-1-4684-6009-4_11. etal. Advances in Experimental Medicine and Biology . 978-1-4684-6011-7 .
• Watorek W . Azurocidin -- inactive serine proteinase homolog acting as a multifunctional inflammatory mediator. . Acta Biochim. Pol. . 50 . 3 . 743–52 . 2004 . 10.18388/abp.2003_3665 . 14515154 . free .
• Zimmer M, Medcalf RL, Fink TM . Three human elastase-like genes coordinately expressed in the myelomonocyte lineage are organized as a single genetic locus on 19pter. . Proc. Natl. Acad. Sci. U.S.A. . 89 . 17 . 8215–9 . 1992 . 1518849 . 10.1073/pnas.89.17.8215 . 49888 . 1992PNAS...89.8215Z . etal. free .
• Green BG, Weston H, Ashe BM . PMN elastases: a comparison of the specificity of human isozymes and the enzyme from other species toward substrates and inhibitors. . Arch. Biochem. Biophys. . 286 . 1 . 284–92 . 1991 . 1897955 . 10.1016/0003-9861(91)90042-H . etal.
• Flodgaard H, Ostergaard E, Bayne S . Covalent structure of two novel neutrophile leucocyte-derived proteins of porcine and human origin. Neutrophile elastase homologues with strong monocyte and fibroblast chemotactic activities. . Eur. J. Biochem. . 197 . 2 . 535–47 . 1991 . 2026172 . 10.1111/j.1432-1033.1991.tb15942.x . etal.
• Almeida RP, Melchior M, Campanelli D . Complementary DNA sequence of human neutrophil azurocidin, an antibiotic with extensive homology to serine proteases. . Biochem. Biophys. Res. Commun. . 177 . 2 . 688–95 . 1991 . 2049091 . 10.1016/0006-291X(91)91843-2 . etal. free .
• Pohl J, Pereira HA, Martin NM, Spitznagel JK . Amino acid sequence of CAP37, a human neutrophil granule-derived antibacterial and monocyte-specific chemotactic glycoprotein structurally similar to neutrophil elastase. . FEBS Lett. . 272 . 1–2 . 200–4 . 1990 . 2226832 . 10.1016/0014-5793(90)80484-Z . 36779510 . free .
• Campanelli D, Detmers PA, Nathan CF, Gabay JE . Azurocidin and a homologous serine protease from neutrophils. Differential antimicrobial and proteolytic properties . J. Clin. Invest. . 85 . 3 . 904–15 . 1990 . 2312733 . 10.1172/JCI114518 . 296509 .
• Pereira HA, Shafer WM, Pohl J . CAP37, a human neutrophil-derived chemotactic factor with monocyte specific activity . J. Clin. Invest. . 85 . 5 . 1468–76 . 1990 . 2332502 . 10.1172/JCI114593 . 296594 . etal.
• Wilde CG, Snable JL, Griffith JE, Scott RW . Characterization of two azurphil granule proteases with active-site homology to neutrophil elastase . J. Biol. Chem. . 265 . 4 . 2038–41 . 1990 . 10.1016/S0021-9258(19)39936-3 . 2404977 . free .
• Pereira HA, Spitznagel JK, Pohl J . CAP 37, a 37 kD human neutrophil granule cationic protein shares homology with inflammatory proteinases . Life Sci. . 46 . 3 . 189–96 . 1990 . 2406527 . 10.1016/0024-3205(90)90104-Y . etal.
• Gabay JE, Scott RW, Campanelli D . Antibiotic proteins of human polymorphonuclear leukocytes . Proc. Natl. Acad. Sci. U.S.A. . 86 . 14 . 5610–4 . 1989 . 2501794 . 10.1073/pnas.86.14.5610 . 297672 . 1989PNAS...86.5610G . etal. free .
• Pereira HA, Erdem I, Pohl J, Spitznagel JK . Synthetic bactericidal peptide based on CAP37: a 37-kDa human neutrophil granule-associated cationic antimicrobial protein chemotactic for monocytes . Proc. Natl. Acad. Sci. U.S.A. . 90 . 10 . 4733–7 . 1993 . 8506327 . 10.1073/pnas.90.10.4733 . 46587 . 1993PNAS...90.4733P . free .
• Chertov O, Michiel DF, Xu L . Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils . J. Biol. Chem. . 271 . 6 . 2935–40 . 1996 . 8621683 . 10.1074/jbc.271.6.2935 . etal. free .
• Iversen LF, Kastrup JS, Bjørn SE . Structure of HBP, a multifunctional protein with a serine proteinase fold . Nat. Struct. Biol. . 4 . 4 . 265–8 . 1997 . 9095193 . 10.1038/nsb0497-265 . 19949043 . etal.
• Karlsen S, Iversen LF, Larsen IK . Atomic resolution structure of human HBP/CAP37/azurocidin . Acta Crystallogr. D . 54 . Pt 4 . 598–609 . 1998 . 9761855 . 10.1107/S0907444997016193 . 1998AcCrD..54..598K . etal.
• Olofsson AM, Vestberg M, Herwald H . Heparin-binding protein targeted to mitochondrial compartments protects endothelial cells from apoptosis . J. Clin. Invest. . 104 . 7 . 885–94 . 1999 . 10510329 . 10.1172/JCI6671 . 408551 . etal.
• Lindmark A, Garwicz D, Rasmussen PB . Characterization of the biosynthesis, processing, and sorting of human HBP/CAP37/azurocidin . J. Leukoc. Biol. . 66 . 4 . 634–43 . 1999 . 10534120 . 10.1002/jlb.66.4.634. 27897421 . etal.

Notes and References

1. Morgan JG, Sukiennicki T, Pereira HA, Spitznagel JK, Guerra ME, Larrick JW . Cloning of the cDNA for the serine protease homolog CAP37/azurocidin, a microbicidal and chemotactic protein from human granulocytes . J Immunol . 147 . 9 . 3210–4 . Nov 1991 . 10.4049/jimmunol.147.9.3210 . 1919011 . free .
2. Web site: Entrez Gene: AZU1 azurocidin 1 (cationic antimicrobial protein 37).
3. Soehnlein. Oliver. Lindbom. Lennart. 2009. Neutrophil-derived azurocidin alarms the immune system. Journal of Leukocyte Biology. en. 85. 3. 344–351. 10.1189/jlb.0808495. 18955543. 23637918. 1938-3673. free.
4. Iversen. L. F.. Kastrup. J. S.. Bjørn. S. E.. Rasmussen. P. B.. Wiberg. F. C.. Flodgaard. H. J.. Larsen. I. K.. 1997. Structure of HBP, a multifunctional protein with a serine proteinase fold. Nature Structural Biology. 4. 4. 265–268. 1072-8368. 9095193. 10.1038/nsb0497-265. 19949043.
5. Linder A, Christensson B, Herwald H, Björck L, Akesson P . Heparin-binding protein: an early marker of circulatory failure in sepsis . Clin. Infect. Dis. . 49 . 7 . 1044–50 . October 2009 . 19725785 . 10.1086/605563 . free .