Biology:Azurocidin 1
Generic protein structure example |
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.[2]
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]
References
- ↑ "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. PMID 1919011.
- ↑ 2.0 2.1 "Entrez Gene: AZU1 azurocidin 1 (cationic antimicrobial protein 37)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=566.
- ↑ Soehnlein, Oliver; Lindbom, Lennart (2009). "Neutrophil-derived azurocidin alarms the immune system" (in en). Journal of Leukocyte Biology 85 (3): 344–351. doi:10.1189/jlb.0808495. ISSN 1938-3673. PMID 18955543.
- ↑ 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. doi:10.1038/nsb0497-265. ISSN 1072-8368. PMID 9095193.
- ↑ "Heparin-binding protein: an early marker of circulatory failure in sepsis". Clin. Infect. Dis. 49 (7): 1044–50. October 2009. doi:10.1086/605563. PMID 19725785.
External links
- Human AZU1 genome location and AZU1 gene details page in the UCSC Genome Browser.
Further reading
- "Human neutrophil granule cationic protein CAP37 is a specific macrophage chemotaxin that shares homology with inflammatory proteinases.". Adv. Exp. Med. Biol.. Advances in Experimental Medicine and Biology 305: 89–96. 1992. doi:10.1007/978-1-4684-6009-4_11. ISBN 978-1-4684-6011-7. PMID 1755383.
- Watorek W (2004). "Azurocidin -- inactive serine proteinase homolog acting as a multifunctional inflammatory mediator.". Acta Biochim. Pol. 50 (3): 743–52. doi:10.18388/abp.2003_3665. PMID 14515154.
- "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. doi:10.1073/pnas.89.17.8215. PMID 1518849. Bibcode: 1992PNAS...89.8215Z.
- "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. doi:10.1016/0003-9861(91)90042-H. PMID 1897955.
- "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. doi:10.1111/j.1432-1033.1991.tb15942.x. PMID 2026172.
- "Complementary DNA sequence of human neutrophil azurocidin, an antibiotic with extensive homology to serine proteases.". Biochem. Biophys. Res. Commun. 177 (2): 688–95. 1991. doi:10.1016/0006-291X(91)91843-2. PMID 2049091.
- "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. doi:10.1016/0014-5793(90)80484-Z. PMID 2226832.
- "Azurocidin and a homologous serine protease from neutrophils. Differential antimicrobial and proteolytic properties". J. Clin. Invest. 85 (3): 904–15. 1990. doi:10.1172/JCI114518. PMID 2312733.
- "CAP37, a human neutrophil-derived chemotactic factor with monocyte specific activity". J. Clin. Invest. 85 (5): 1468–76. 1990. doi:10.1172/JCI114593. PMID 2332502.
- "Characterization of two azurphil granule proteases with active-site homology to neutrophil elastase". J. Biol. Chem. 265 (4): 2038–41. 1990. doi:10.1016/S0021-9258(19)39936-3. PMID 2404977.
- "CAP 37, a 37 kD human neutrophil granule cationic protein shares homology with inflammatory proteinases". Life Sci. 46 (3): 189–96. 1990. doi:10.1016/0024-3205(90)90104-Y. PMID 2406527.
- "Antibiotic proteins of human polymorphonuclear leukocytes". Proc. Natl. Acad. Sci. U.S.A. 86 (14): 5610–4. 1989. doi:10.1073/pnas.86.14.5610. PMID 2501794. Bibcode: 1989PNAS...86.5610G.
- "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. doi:10.1073/pnas.90.10.4733. PMID 8506327.
- "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. doi:10.1074/jbc.271.6.2935. PMID 8621683.
- "Structure of HBP, a multifunctional protein with a serine proteinase fold". Nat. Struct. Biol. 4 (4): 265–8. 1997. doi:10.1038/nsb0497-265. PMID 9095193.
- "Atomic resolution structure of human HBP/CAP37/azurocidin". Acta Crystallogr. D 54 (Pt 4): 598–609. 1998. doi:10.1107/S0907444997016193. PMID 9761855.
- "Heparin-binding protein targeted to mitochondrial compartments protects endothelial cells from apoptosis". J. Clin. Invest. 104 (7): 885–94. 1999. doi:10.1172/JCI6671. PMID 10510329.
- "Characterization of the biosynthesis, processing, and sorting of human HBP/CAP37/azurocidin". J. Leukoc. Biol. 66 (4): 634–43. 1999. doi:10.1002/jlb.66.4.634. PMID 10534120.