Human β-defensins

Pazgier, M.; Hoover, David M.; Yang, De; Lu, Weiyue; Łubkowski, J.

doi:10.1007/s00018-005-5540-2

Cited by 464 publications

(449 citation statements)

References 209 publications

(474 reference statements)

Supporting

Mentioning

427

Contrasting

Unclassified

Order By: Relevance

“…Apart from plectasin and micasin, eurocin is the only fungal defensin with a known threedimensional structure. Mammalian defensins belong to a different structural family (54,55), e.g. human ␤-defensin-2, which consists of a helical segment and a three-stranded ␤-sheet (54).…”

Section: Discussionmentioning

confidence: 99%

Eurocin, a New Fungal Defensin

Oeemig

Lynggaard

Knudsen

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Antimicrobial peptides are new antibiotics avoiding resistance problems. Results: Eurocin is a new antimicrobial peptide featuring a cysteine-stabilized ␣␤-fold. Eurocin binds the cell wall precursor lipid II but does not disrupt cell membranes. Conclusion: Eurocin acts by inhibiting cell wall synthesis. Its structure is typical for invertebrate defensins. Significance: Knowing the mode of action and structure is a prerequisite for pharmaceutical application of an antibiotic.

show abstract

Section: Discussionmentioning

confidence: 99%

Eurocin, a New Fungal Defensin

Oeemig

Lynggaard

Knudsen

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In each case, results were averaged over three independent experiments, and values of standard errors were determined. The final results are expressed as LD 50 , LD 90 , and LD 99 , representing the concentrations of defensins causing death of 50, 90, and 99% of E. coli cells, respectively.…”

Section: Methodsmentioning

confidence: 99%

Studies of the Biological Properties of Human β-Defensin 1

Pazgier

Prahl²,

Hoover³

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

Defensins are small (30 -45 amino acid residues) cationic proteins with broad antimicrobial activity against many bacteria and fungi, some enveloped viruses, and other activities such as chemoattraction of a range of different cell types to the sites of inflammation. These proteins represent attractive targets for developing novel antimicrobial agents and modulators of immune responses with therapeutic applicability. In this report, we present the results of functional and structural studies of 26 single-site mutants of human ␤-defensin 1 (hBD1). All mutants were assayed for antimicrobial activity against Escherichia coli (ATCC strain 25922) and for chemotactic activity with CCR6-transfected HEK293 cells. To analyze the structural implications of mutagenesis and to verify the correctness of the disulfide connectivity, we used x-ray crystallography to conduct complete structural studies for 10 mutants in which the topology of disulfides was the same as in the native hBD1. Mutations did not induce significant changes of the tertiary structure, suggesting that the observed alterations of biological properties of the mutants were solely associated with changes in the respective side chains. We found that cationic residues located near the C terminus (Arg Defensins are recognized as an important element of the human innate immune system (1-4). The defensin family is composed of small (3-5 kDa), cationic, and cysteine-rich proteins. In human defensins, the connectivity of three disulfide bridges forms the basis for assigning them into one of two classes, the ␣-and ␤-defensins (5-7). In ␤-defensins, the topology of the three disulfide bridges is 1-5, 2-4, and 3-6, meaning that the first cysteine in the sequence is covalently linked to the fifth, and so on. Three human ␤-defensins, hBD1-3, 4 have been isolated from natural sources and characterized in detail (8 -11). Additionally, the recombinant or synthetic preparations of hBD4, hBD27, and hBD28 have also been described and characterized functionally (12, 13). Analysis of the human genome indicates the existence of over 40 potential coding regions for these peptides (14,15).In addition to broad antimicrobial activity, hBDs have also been recognized as modulators of cell-mediated adaptive immunity, due to their chemotactic and immunoenhancing activity (16 -19). Recent studies revealed that ␤-defensins also play a role in cell differentiation, tissue remodeling, and sperm maturation (20 -22).The first human ␤-defensin to be discovered, hBD1, is constitutively expressed in the epithelial cells of the urinary and respiratory tracts and in keratinocytes of skin (9,23,24). A naturally occurring 36-amino acid hBD1 peptide shows anti-bacterial activity at micromolar concentrations against some Gramnegative bacteria (i.e. Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae), as well as yeast Candida albicans. When tested in vitro, hBD1 is relatively less potent against the Gram-positive Streptococcus aureus (9, 10, 23).HBD1 and hBD2 selectively chemoattract hum...

show abstract

“…Various peptides of the b-defensin family are involved in and mediate various biological processes based on their pleiotropic activities. [2][3][4][5][6][7][8][9] A number of these processes are beyond immune-related events; these include cell differentiation, tumour development, tissue remodelling 10 and sperm maturation. 11 Nonetheless, the roles of most of the b-defensins that are prevalently expressed in the epididymis are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Rat recombinant β-defensin 22 is a heparin-binding protein with antimicrobial activity

Diao¹,

Yu²,

Sun³

et al. 2010

Asian J Androl

View full text Add to dashboard Cite

Approximately 40-50 b-defensins are predominantly expressed in the male reproductive system of mammals. This selective expression raises the question as to the roles of these molecules in innate immunity and fertility in the male reproductive tract. Rat b-defensin 22 is an epididymis-specific b-defensin expressed in segments 12-14 of the epididymis. This protein contains both b-defensin and lectin signature sequences, yet its antimicrobial activity and carbohydrate-binding ability have not been shown. We herein demonstrated the antimicrobial activity of recombinant rat b-defensin 22 against Escherichia coli and Candida albicans. Its lectin-like activity was also investigated by demonstrating its binding ability with heparin beads. This heparin-binding activity implies some potential roles for this defensin in determining the fertilisation capabilities of sperm.

show abstract

Human β-defensins

Cited by 464 publications

References 209 publications

Eurocin, a New Fungal Defensin

Eurocin, a New Fungal Defensin

Studies of the Biological Properties of Human β-Defensin 1

Rat recombinant β-defensin 22 is a heparin-binding protein with antimicrobial activity

Contact Info

Product

Resources

About