Antimicrobial Peptide AP00433

     
 

APD ID:

AP00433

 
 

Name/Class:

Dermcidin (DCD-1; human, primates, mammals, animals; Variants and derivatives: DCD-1L; SSL-23; SSL-25; SSL-29. JJ5)

 
 

Source:

Eccrine sweat glands, skin, Homo sapiens

 
 

Sequence:

SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSV

 
 

Length:

47

 
 

Net charge:

-2

 
 

Hydrophobic residue%:

38%

 
 

Boman Index:

1.11 kcal/mol

 
 

3D Structure:

Helix

 
 

Method:

X-ray

 
 

SwissProt ID:

PDB ID: 2YMK   Go to PDB

 
 

Activity:

Anti-Gram+ & Gram-, Antifungal,

 
 

Additional info:

Constitutively expressed in human sweat glands (1-10 ug/mL). Deficiency in dermcidin-derived peptides in human sweat of AD patients correlates with impaired innate defense in skin (Rieg S et al. 2005 J Immunol 174: 8003-10). In vitro MIC against E. coli, E. faecalis and S. aureus at ~1 ug.mL, and at 10 ug.mL C. albicans. Also active against P. acnes (ref). A variant DLD-1L, with one additional leucine at the C-terminus, showed similar antimicorbial activites but appeared to be more sensitive to salt conditions (salt-sensitive). N-terminal cationic fragments SSL-23 and SSL-25 are active against both a select set of G+ and G- bacteria. However, a 30-residue C-terminal fragment and a N-terminal 29mer (SSL-29, neutral) were found to be inactive. (MOA) This anionic peptide DCD may kill microbes by targeting bacterial envelope in a mechanism different from that of cationic LL-37 (Steffen H et al 2006 Antimicrob Agents Chemother 50: 2608-2620). NMR+x: NMR structural analysis of dermcidin-1L in 50% TFE using an N15-labeled recombinant peptide reveals a long helix-hinge-helix motif, allowing it to associate with bacterial membranes (Jung et al. 2010 BMB Rep. 43: 362-8) (View NMR structure). In 2013, the crystal structure of dermcidin was also reported (Visit the PDB link). You can rotate, zoom, and view the hexameric crystal structure here in the PDB. A channel was proposed based on the crystal structure. (Resistance problem) The decreased sensitivity of P. aeruginosa to DCD-derived peptides is not mediated by proteolytic degradation under physiological conditions (Int J Antimicrob Agents. 2009 Feb 6). For a review of dermcidin, please refer to Schittek B (2012) The multiple facets of dermcidin in cell survival and host defense. J Innate Immun March 27 online. Notably, in melanoma, dermcidin is over-expressed. Selectively targeting dermcidin with a small molecule seriniquinone led to cancer cell death (Trzoss L et al., 2014). Update 4/2012, 9/2013; 11/2014 GW.

 
       
 

Title:

Dermcidin: a novel human antibiotic peptide secreted by sweat glands.

 
 

Author:

Schittek B., Hipfel R., Sauer B., Bauer J., Kalbacher H., Stevanovic S., Schirle M., Schroeder K., Blin N., Meier F., Rassner G., Garbe C.2001

 
 

Reference:

Nat. Immunol. 2001; 2:1133-1137. PubMed

 
       

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