6dmq

Crystal structure of the T27A mutant of human alpha defensin HNP4.

spinqualitylabelsall models 6dmq, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6dmq is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Ligands: MPD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DEF4_HUMAN Has antimicrobial activity against Gram-negative bacteria, and to a lesser extent also against Gram-positive bacteria and fungi. Protects blood cells against infection with HIV-1 (in vitro). Inhibits corticotropin (ACTH)-stimulated corticosterone production. Publication Abstract from PubMed Defensins are a family of cationic antimicrobial peptides of innate immunity with immunomodulatory properties. The prototypic human alpha-defensins, also known as human neutrophil peptides 1-3 or HNP1-3, are extensively studied for their structure, function and mechanisms of action, yet little is known about HNP4 - the much less abundant "distant cousin" of HNP1-3. Here we report a systematic mutational analysis of HNP4 with respect to its antibacterial activity against E. coli and S. aureus, inhibitory activity against anthrax lethal factor (LF), and binding activity for LF and HIV-1 gp120. Except for nine conserved and structurally important residues (6xCys, 1xArg, 1xGlu and 1xGly), the remaining 24 residues of HNP4 were each individually mutated to Ala. The crystal structures of G23A-HNP4 and T27A-HNP4 were determined, both exhibiting a disulfide-stabilized canonical alpha-defensin dimer identical to wild-type HNP4. Unlike HNP1-3, HNP4 preferentially killed the Gram-negative bacterium, a property largely attributable to three clustered cationic residues Arg10, Arg11 and Arg15. The cationic cluster was also important for HNP4 killing of S. aureus, inhibition of LF and binding to LF and gp120. However, F26A, while functionally inconsequential for E. coli killing, was far more deleterious than any other mutations. Similarly, N-methylation of Leu20 to destabilize the HNP4 dimer had little effect on E. coli killing, but significantly reduced the ability of HNP4 to kill S. aureus, inhibit LF, and bind to LF and gp120. Our findings unveil the molecular determinants of HNP4 function, completing the atlas of structure and function relationships for all human neutrophil alpha-defensins. Systematic mutational analysis of human neutrophil alpha-defensin HNP4.,Hu H, Di B, David Tolbert W, Gohain N, Yuan W, Gao P, Ma B, He Q, Pazgier M, Zhao L, Lu W Biochim Biophys Acta Biomembr. 2019 Jan 15. pii: S0005-2736(19)30010-0. doi:, 10.1016/j.bbamem.2019.01.007. PMID:30658057 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Defensin 3D structures

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