Antimicrobial Peptide AP00445

     
 

APD ID:

AP00445

 
 

Name/Class:

RTD-1 (rhesus theta defensin-1; monkey, primates, mammals, animals; 3S=S, Cys-rich; XXC, UCBB1b; BBS, ZZHa; BBBH2o; revisited)

 
 

Source:

leukocytes, Rhesus Macaque (Macaca mulatta)

 
 

Sequence:

GFCRCLCRRGVCRCICTR

 
 

Length:

18

 
 

Net charge:

5

 
 

Hydrophobic residue%:

55%

 
 

Boman Index:

2.81 kcal/mol

 
 

3D Structure:

Beta

 
 

Method:

NMR

 
 

SwissProt ID:

PDB ID: 2LYF   Go to PDB

 
 

Activity:

Anti-Gram+ & Gram-, Antiviral, Antifungal, Anti-HIV, Anti-MRSA, Anti-toxin,

 
 

Crucial residues:

Circular structure, S-S bonds, and Arg residues important for activity and salt insensitivity.

 
 

Additional info:

Active against S. aureus 502a (including MRSA), L. monocytogenes, E. coli ML 35, S. typhimurium, C. albicans 16820, and C. neoformans. The first theta-defensin reported. It is a two gene ligation product. RTD-1 is most abundant (~50% of the RTD content; the ratio of RTD1, -2, and 3 are 29:1:2). Total RTD content varied by 3 fold between animals (see ref for AP1074). It contains three disulfide bonds: 3,16; 5,14; 7,12. The molecule self associates in water in a concentration-depedent manner. Initially thought flexible (PDB ID: 1HVZ), the refined 3D structure revealed a rigid beta-hairpin structure (PDB ID: 2LYF; Conibear AC et al., 2012). You can rotate, zoom, and view the refined 3D structure here in the PDB. Antibacterial activity of this circular molecule is salt-insensitive compared to non-circular alpha-defensins. The antibacterial activity of synthetic and isolated forms is indistinguishable. Acyclic RTD peptides are substantially less active against E. coli and S. aureus. MOA1: Theta-defensins are internalized rapidly by target bacterial cells. Theta-defensins are particularly important for antifungal activity of the granule extracts as alpha-defensins are poorly active (Tongaonkar P et al 2011 J Leuko Biol in press). It is also active against HIV-1. MOA2: it binds to gp120 and CD4, thereby inhibiting HIV entry (Wang W J Immunol 2004; 173:515-520). RTD-1 showed efficacy in animal model:mouse of severe acute respiratory syndrome coronavirus (SARS) pulmonary disease (Wohlford-Lenane CL et al. 2009 J Virol 83: 11385-90). APD update: 6/2012, 11/2012; 9/2017 GW.

 
       
 

Title:

A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins

 
 

Author:

Tang YQ, Yuan J, Osapay G, Osapay K, Tran D, Miller CJ, Ouellette AJ, Selsted ME1999

 
 

Reference:

Science. 1999 Oct 15;286(5439):498-502

 
       

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