2itf | pdb_00002itf
Crystal structure IsdA NEAT domain from Staphylococcus aureus with heme bound
Structural highlights
FunctionISDA_STAA8 Cell wall-anchored surface receptor that participates in the extraction of heme from oxidized methemoglobin/metHb to enable growth on hemoglobin as a sole iron source (By similarity). Receives heme from IsdB and transfers it to IsdC (By similarity). Also plays a role in the inhibition of host immune response. Protects S.aureus against the bactericidal protease activity of apolactoferrin. Decreases bacterial cellular hydrophobicity, which renders S.aureus resistant to bactericidal human skin fatty acids as well as to beta-defensins and cathelicidin. Also binds fibronectin and chains B-beta and gamma of fibrinogen, promoting clumping of S.aureus with fibrinogen. Involved in adherence of S.aureus to human desquamated nasal epithelial cells and is required for nasal colonization (By similarity).[UniProtKB:A6QG31][UniProtKB:Q7A152] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSuccessful pathogenic organisms have developed mechanisms to thrive under extreme levels of iron restriction. Haem-iron represents the largest iron reservoir in the human body and is a significant source of iron for some bacterial pathogens. NEAT (NEAr Transporter) domains are found exclusively in a family of cell surface proteins in Gram-positive bacteria. Many NEAT domain-containing proteins, including IsdA in Staphylococcus aureus, are implicated in haem binding. Here, we show that overexpression of IsdA in S. aureus enhances growth and an inactivation mutant of IsdA has a growth defect, compared with wild type, when grown in media containing haem as the sole iron source. Furthermore, the haem-binding property of IsdA is contained within the NEAT domain. Crystal structures of the apo-IsdA NEAT domain and in complex with haem were solved and reveal a clathrin adapter-like beta-sandwich fold with a large hydrophobic haem-binding pocket. Haem is bound with the propionate groups directed at the molecular surface and the iron is co-ordinated solely by Tyr(166). The phenol groups of Tyr(166) and Tyr(170) form an H-bond that may function in regulating haem binding and release. An analysis of IsdA structure-sequence alignments indicate that conservation of Tyr(166) is a predictor of haem binding by NEAT domains. Haem recognition by a Staphylococcus aureus NEAT domain.,Grigg JC, Vermeiren CL, Heinrichs DE, Murphy ME Mol Microbiol. 2007 Jan;63(1):139-49. PMID:17229211[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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