5WRX

VG13P structure in LPS

Summary for 5WRX

• Entry DOI: 10.2210/pdb5wrx/pdb
• NMR Information: BMRB: 36038
• Descriptor: analogue peptide VG13P (1 entity in total)
• Functional Keywords: antimicrobial peptide, endotoxin neutralisation, turn and loop-like structure, de novo protein, antimicrobial protein
• Biological source: SYNTHETIC CONSTRUCT
• Total number of polymer chains: 1
• Total formula weight: 1449.74

Authors

Datta, A.,Bhunia, A. (deposition date: 2016-12-04, release date: 2017-05-10, Last modification date: 2024-05-15)

Primary citation

Datta, A.,Jaiswal, N.,Ilyas, H.,Debnath, S.,Biswas, K.,Kumar, D.,Bhunia, A.
Structural and Dynamic Insights into a Glycine-Mediated Short Analogue of a Designed Peptide in Lipopolysaccharide Micelles: Correlation Between Compact Structure and Anti-Endotoxin Activity.
Biochemistry, 56:1348-1362, 2017

PubMed Abstract: In this study, we report an interaction study of a 13-residue analogue peptide VG13P (VARGWGRKCPLFG), derived from a designed VG16KRKP peptide (VARGWKRKCPLFGKGG), with a Lys6Gly mutation and removal of the last three residues Lys-Gly-Gly, in lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria and responsible for sepsis or septic shock. VG13P displays an enhanced anti-endotoxin property as evident from significant reduction in LPS-induced TNF-α gene expression levels in a monocytic cell line, while it retains almost unchanged antimicrobial activity as its parent VG16KRKP against Gram-negative bacterial as well as fungal pathogens. In addition, in vitro LPS binding properties of VG13P in comparison to its parent VG16KRKP also remained unhindered, suggesting that the flexible C-terminal end of VG16KRKP may not play a major role in its observed antibacterial and LPS binding properties. An NMR-resolved solution structure of VG13P in LPS reveals two consecutive β-turns: one at the N-terminus, followed by another at the central region, closely resembling a rocking chair. The crucial Lys6Gly mutation along with C-terminal truncation from VG16KRKP reorients the hydrophobic hub in VG13P in a unique way so as to fold the N-terminal end back on itself, forming a turn and allowing Val1 and Ala2 to interact with Leu11 and Phe12 to bring the hydrophobic residues closer together to form a more compact hub compared to its parent. The hub is further strengthened via CH-π interaction between Gly4 and Phe12. This accounts for its improved anti-endotoxin activity as well as to its uninterrupted antimicrobial activity.

PubMed: 28168875
DOI: 10.1021/acs.biochem.6b01229

Experimental method

SOLUTION NMR