Antimicrobial Peptide AP00451“>004512481.61 %100.0 %AVP
     
 

APD ID:

AP00451

 
 

Name/Class:

hBD-1 (Human beta-defensin 1; hBD1; 3S=S; UCSS1a; primates, mammals, animals; ZZH, JJsn; XXR)

 
 

Source:

hemofiltrates, urine, kidney; keratinocytes; skin; platelets; oral saliva; milk, mammary gland epithelium, Homo sapiens

 
 

Sequence:

DHYNCVSSGGQCLYSACPIFTKIQGTCYRGKAKCCK

 
 

Length:

36

 
 

Net charge:

4

 
 

Hydrophobic residue%:

36%

 
 

Boman Index:

1.3 kcal/mol

 
 

3D Structure:

Combine Helix and Beta structure

 
 

Method:

NMR

 
 

SwissProt ID:

PDB ID: 1E4S   Go to PDB

 
 

Activity:

Anti-Gram+ & Gram-, Antiviral, Anti-HIV, Anti-toxin, Channel inhibitors, Anticancer

 
 

Additional info:

The first human beta defensin found. Expression: hBD-1 is constitutively expressed.

Activity:While the reduced form is active against both Gram+ and Gram- bacteria, the oxidized form is only active against Gram- bacteria with little effect on cell envelope (Raschig J et al., 2017). hBD-1 is one of the most prominent peptides of its class but despite ubiquitous expression by all human epithelia, comparison with other defensins suggested only minor antibiotic killing activity. Interestingly, it inhibits the growth of clinical S. aureus strains but NOT lab strains. It was observed that hBD-1 from human platelets can cluster bacteria and signals NETs formation (Kraemer BF et al. 2011 PLoS Pathog Nov 7). This AMP is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis (Cell. 1997 Feb 21;88(4):553-60). It is VERY interesting that after reduction of disulphide-bridges, hBD-1 becomes a potent AMP against the opportunistic pathogenic fungus C. albicans and against anaerobic, Gram-positive commensals of Bifidobacterium and Lactobacillus species. It seems to work using a different mechanism from hBD-3 (mainly on membranes). For a full story, please refer to Schroeder BO et al Reduction of disulphide bonds unmasks potent antimicrobial activity of human beta-defensin 1 Nature. 2011 Jan 20;469(7330):419-23 (APD recommended reading). Apoptosis. This AMP shows synergistic effect with LL-37 or lysozyme against S. aureus and E. coli (Chen X et al 2005 J Dermatol Sci 40: 123-32).

Structure nmr+x: it contains one helix and three beta-strands linked by three disulfide bonds (NMR: Bauer F et al. 2001 Protein Sci 10:2470, use the PDB link; X-ray: Hoover DM et al 2001 J Biol Chem 276:39021-6; PDB: 1IJV). You can rotate, zoom, and view the NMR structure here in the PDB . You can view the crystal structure here.

Chemotactic: chemotactic effects of hBD-1 is achieved via the CCR6 receptor expressed on immature dendritic cells and CD45RO+ and CD4+ T cells (Pazgier M et al., 2007). The CCR6-mediated chemotaxis surface is defined by the N-terminal alpha-helical region (Asp(1)... Ser(8)) and a few topologically adjacent residues (Lys(22), Arg(29), and Lys(33)).

Channel inhibitor: HBD1 was found to selectively inhibit human and mouse Kv1.3 channels with IC50 values of 11.8 3.1 uM and 13.2 4.0 uM, respectively (Feng J et al., 2016).

Relationship with human diseases High hBD-1 is an accurate predictor of short-term mortality in patients with acute-on-chronic liver failure (ACLF) (Mani et al., 2018). In colonic epithelial cells, hBD-1 is supressed by the EGFR-ERK-MYC axis (Bonamy et al., 2018). APD Updated Jan2011; 11/2011; 4/2016; 3/2017; 9/2018; 11/2018; 12/2018.

 
       
 

Title:

hBD-1: a novel beta-defensin from human plasma

 
 

Author:

Bensch KW, Raida M, Mgert HJ, Schulz-Knappe P, Forssmann WG.1995

 
 

Reference:

FEBS Lett. 1995 Jul 17;368(2):331-5

 
       

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