Please use this identifier to cite or link to this item: https://doi.org/10.1038/emboj.2009.380
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dc.titleRapid reprogramming of haemoglobin structure-function exposes multiple dual-antimicrobial potencies
dc.contributor.authorDu, R.
dc.contributor.authorHo, B.
dc.contributor.authorDing, J.L.
dc.date.accessioned2014-10-27T08:38:06Z
dc.date.available2014-10-27T08:38:06Z
dc.date.issued2010-02
dc.identifier.citationDu, R., Ho, B., Ding, J.L. (2010-02). Rapid reprogramming of haemoglobin structure-function exposes multiple dual-antimicrobial potencies. EMBO Journal 29 (3) : 632-642. ScholarBank@NUS Repository. https://doi.org/10.1038/emboj.2009.380
dc.identifier.issn02614189
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/101522
dc.description.abstractThe intrinsic cytotoxicity of cell-free haemoglobin (Hb) has hampered the development of reliable Hb-based blood substitutes for over seven decades. Notably, recent evidence shows that the Hb deploys this cytotoxic attack against invading microbes, albeit, through an unknown mechanism. Here, we unraveled a rapid molecular reprogramming of the Hb structure-function triggered by virulent haemolytic pathogens that feed on the haem-iron. On direct contact with the microbe, the Hb unveils its latent antimicrobial potency, where multiple antimicrobial fragments are released, each harbouring coordinated dual-action centres: microbe binding and pseudoperoxidase (POX) cycle activity. The activated Hb fragments anchor onto the microbe while the juxtaposed POX instantly unleashes a localized oxidative shock, killing the pathogen-in-proximity. This concurrent action conceivably restricts the diffusion of free radicals. Furthermore, the host astutely protects itself from self-cytotoxicity by simultaneously releasing endogenous antioxidants. We found that this decryption mechanism of antimicrobial potency is conserved in the ancient invertebrate respiratory protein, indicating its fundamental significance. Our definition of dual-antimicrobial centres in the Hb provides vital clues for designing a safer Hb-based oxygen carrier blood substitute. © 2010 European Molecular Biology Organization | Some Rights Reserved.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1038/emboj.2009.380
dc.sourceScopus
dc.subjectDual-antimicrobial activity
dc.subjectHaemoglobin free radicals
dc.subjectLimited proteolysis
dc.subjectMicrobe-binding and oxidative shock
dc.subjectReprogramming structure-function of haemoglobin
dc.typeArticle
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.description.doi10.1038/emboj.2009.380
dc.description.sourcetitleEMBO Journal
dc.description.volume29
dc.description.issue3
dc.description.page632-642
dc.description.codenEMJOD
dc.identifier.isiut000274233400011
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