Antimicrobial Peptide AP00729

     
 

APD ID:

AP00729

 
 

Name/Class:

Kalata B1 (KB1; XXC; cyclotides; UCBB1b; 3S=S; plants; ZZHp; ZZi; BBMm; BBBm; Derivatives: kalata B1 oia or nfk; XXO)

 
 

Source:

African herb, Oldenlandia affinis

 
 

Sequence:

GLPVCGETCVGGTCNTPGCTCSWPVCTRN

 
 

Length:

29

 
 

Net charge:

0

 
 

Hydrophobic residue%:

37%

 
 

Boman Index:

0.67 kcal/mol

 
 

3D Structure:

Beta

 
 

Method:

X-ray

 
 

SwissProt ID:

PDB ID: 4TTM   Go to PDB

 
 

Activity:

anti-Gram+, antiviral, Insecticidal, anti-HIV, Enzyme inhibitor, Hemolytic,

 
 

Crucial residues:

circular structure; G6 is critical to bind phosphatidylethanolamine (Hall et al., 2012 Biochim Biophys Acta 1818:2354).

 
 

Additional info:

First isolated by Gran in 1973 (Acta Pharmacol Toxicol (Copenh). 1973;33(5):400-8), the circular structure was established in 1995 (Saether O, et al.), and antimicrobial activity was demonstrated in 1999, thereby establishing it as an AMP. Cellular location: accumulated in vacuole and processed likely by asparaginyl endoproteinase (Conlan BF et al. 2011 Am J Bot 98:2018-26). Structure: there are other PDB entries: 1JJZ, 1NB1, and 1ZNU. You can rotate, zoom, and view the 4TTM structure here in the PDB . Antibacterial activity was salt dependent and the peptide was most active against S. aureus (0.26 uM). The overall fold is important for anti-HIV activity, since the acyclic permutant is inactive. Kalata B1 also has uterotonic and insecticidal activity (natural pesticide). (MOA) An all D-analog is also active, supporting membrane targeting (Sando L. et al. 2011 Chembiochem 12: 2456-62). NMR studies of the ternary complex identified amino acid residues in loop 5 (W23, P24, and V25) and loop 6 (L2, P3, and V4) are important for membrane binding (Shenkarrev ZO et al. 2006 FEBS J 273:2658-72). It binds to phosphatidylethanolamine and leads to pore formation (41-70 A) in lipid bilayers (Huang et al 2009 JBC 284: 20699-20707). Oligomerization on the membrane surface could be important for this process. Note that oxidized forms of this peptide have also been reported. Trp can be oxidized to oxindolylalanine I (oia) or N-formylkynurenine (nfk). The effect of such oxidation on activity is unknown (Plan MR et al 2007 Chembiochem 8:1001-11). It also inhibits the human prolyl oligopeptidase (POP) (Hellinger R et al., 2015). Updated 1/15/2010; 11/9/2011; 1/5/2012; 3/25/2012; reference updated 5/1/2013; 2/2016.

 
       
 

Title:

An unusual structural motif of antimicrobial peptides containing end-to-end macrocycle and cystine-knot disulfides.

 
 

Author:

Tam JP, Lu YA, Yang JL, Chiu KW.1999

 
 

Reference:

Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8913-8.PubMed.

 
       

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