1X8U

Crystal structure of Siderocalin (NGAL, Lipocalin 2) complexed with Carboxymycobactin T

Summary for 1X8U

• Entry DOI: 10.2210/pdb1x8u/pdb
• Related: 1X71 1X89
• Descriptor: Neutrophil gelatinase-associated lipocalin, CARBOXYMYCOBACTIN T (3 entities in total)
• Functional Keywords: lipocalin, siderophore, antimicrobial protein
• Biological source: Homo sapiens (human)
• Cellular location: Secreted : P80188
• Total number of polymer chains: 3
• Total formula weight: 64032.22

Authors

Holmes, M.A.,Paulsene, W.,Jide, X.,Ratledge, C.,Strong, R.K. (deposition date: 2004-08-18, release date: 2005-01-25, Last modification date: 2024-10-30)

Primary citation

Holmes, M.A.,Paulsene, W.,Jide, X.,Ratledge, C.,Strong, R.K.
Siderocalin (Lcn 2) Also Binds Carboxymycobactins, Potentially Defending against Mycobacterial Infections through Iron Sequestration
Structure, 13:29-41, 2005

PubMed Abstract: Siderocalin, a member of the lipocalin family of binding proteins, is found in neutrophil granules, uterine secretions, and at markedly elevated levels in serum and synovium during bacterial infection; it is also secreted from epithelial cells in response to inflammation or tumorigenesis. Identification of high-affinity ligands, bacterial catecholate-type siderophores (such as enterochelin), suggested a possible function for siderocalin: an antibacterial agent, complementing the general antimicrobial innate immune system iron-depletion strategy, sequestering iron as ferric siderophore complexes. Supporting this hypothesis, siderocalin is a potent bacteriostatic agent in vitro under iron-limiting conditions and, when knocked out, renders mice remarkably susceptible to bacterial infection. Here we show that siderocalin also binds soluble siderophores of mycobacteria, including M. tuberculosis: carboxymycobactins. Siderocalin employs a degenerate recognition mechanism to cross react with these dissimilar types of siderophores, broadening the potential utility of this innate immune defense.

PubMed: 15642259
DOI: 10.1016/j.str.2004.10.009

Experimental method

X-RAY DIFFRACTION (2.2 Å)