2pms
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(New page: 200px<br /><applet load="2pms" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pms, resolution 2.91Å" /> '''Crystal structure of...)
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Revision as of 11:28, 21 November 2007
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Crystal structure of the complex of human lactoferrin N-lobe and lactoferrin-binding domain of pneumococcal surface protein A
Overview
Human lactoferrin, a component of the innate immune system, kills a wide, variety of microorganisms including the Gram positive bacteria, Streptococcus pneumoniae. Pneumococcal surface protein A (PspA), efficiently inhibits this bactericidal action. The crystal structure of a, complex of the lactoferrin-binding domain of PspA with the N-lobe of human, lactoferrin reveals direct and specific interactions between the, negatively charged surface of PspA helices and the highly cationic, lactoferricin moiety of lactoferrin. Binding of PspA blocks surface, accessibility of this bactericidal peptide preventing it from penetrating, the bacterial membrane. Results of site-directed mutagenesis, in vitro, protein binding assays and isothermal titration calorimetry measurements, corroborate that the specific electrostatic interactions observed in the, crystal structure represent major associations between PspA and, lactoferrin. The structure provides a snapshot of the protective mechanism, utilized by pathogens against the host's first line of defense. PspA, represents a major virulence factor and a promising vaccine candidate., Insights from the structure of the complex have implications for designing, therapeutic strategies for treatment and prevention of pneumococcal, diseases that remain a major public health problem worldwide.
About this Structure
2PMS is a Protein complex structure of sequences from Homo sapiens and Streptococcus pneumoniae with NAG, CO3, FE, SO4 and ZN as ligands. Full crystallographic information is available from OCA.
Reference
Structure of a Complex of Human Lactoferrin N-lobe with Pneumococcal Surface Protein A Provides Insight into Microbial Defense Mechanism., Senkovich O, Cook WJ, Mirza S, Hollingshead SK, Protasevich II, Briles DE, Chattopadhyay D, J Mol Biol. 2007 Jul 20;370(4):701-13. Epub 2007 May 10. PMID:17543335
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