3GNY

Crystal structure of human alpha-defensin 1 (HNP1)

3GNY の概要

• エントリーDOI: 10.2210/pdb3gny/pdb
• 関連するPDBエントリー: 1DFN 2PM1 2PM4 2PM5 3GO0
• 分子名称: Neutrophil defensin 1, CHLORIDE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: antimicrobial peptide, human alpha defensin 1, human neutrophil peptide 1, hnp1, antibiotic, antimicrobial, antiviral defense, defensin, disulfide bond, fungicide, phosphoprotein, secreted, antimicrobial protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted: P59665
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 7123.86

構造登録者

Pazgier, M.,Lu, W.-Y. (登録日: 2009-03-18, 公開日: 2009-07-28, 最終更新日: 2024-11-27)

主引用文献

Wei, G.,de Leeuw, E.,Pazgier, M.,Yuan, W.,Zou, G.,Wang, J.,Ericksen, B.,Lu, W.Y.,Lehrer, R.I.,Lu, W.
Through the looking glass, mechanistic insights from enantiomeric human defensins.
J.Biol.Chem., 284:29180-29192, 2009

PubMed Abstract: Despite the small size and conserved tertiary structure of defensins, little is known at a molecular level about the basis of their functional versatility. For insight into the mechanism(s) of defensin function, we prepared enantiomeric pairs of four human defensins, HNP1, HNP4, HD5, and HBD2, and studied their killing of bacteria, inhibition of anthrax lethal factor, and binding to HIV-1 gp120. Unstructured HNP1, HD5, and HBD3 and several other human alpha- and beta-defensins were also examined. Crystallographic analysis showed a plane of symmetry that related (L)HNP1 and (D)HNP1 to each other. Either d-enantiomerization or linearization significantly impaired the ability of HNP1 and HD5 to kill Staphylococcus aureus but not Escherichia coli. In contrast, (L)HNP4 and (D)HNP4 were equally bactericidal against both bacteria. d-Enantiomers were generally weaker inhibitors or binders of lethal factor and gp120 than their respective native, all-l forms, although activity differences were modest, particularly for HNP4. A strong correlation existed among these different functions. Our data indicate: (a) that HNP1 and HD5 kill E. coli by a process that is mechanistically distinct from their actions that kill S. aureus and (b) that chiral molecular recognition is not a stringent prerequisite for other functions of these defensins, including their ability to inhibit lethal factor and bind gp120 of HIV-1.

PubMed: 19640840
DOI: 10.1074/jbc.M109.018085

実験手法

X-RAY DIFFRACTION (1.56 Å)