4RBW

Crystal structure of human alpha-defensin 5, HD5 (Thr7Arg Glu21Arg mutant)

Summary for 4RBW

• Entry DOI: 10.2210/pdb4rbw/pdb
• Related: 1ZMP 4E82 4E83 4E86 4RBX
• Descriptor: Defensin-5, SULFATE ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: mutant t7r e21r-hd5, beta-sheet, antimicrobial peptide, paneth cells defensin, human alpha-defensin, antimicrobial protein
• Biological source: Homo sapiens (human)
• Cellular location: Secreted : Q01523
• Total number of polymer chains: 4
• Total formula weight: 15649.07

Authors

Pazgier, M.,Gohain, N.,Tolbert, W.D. (deposition date: 2014-09-13, release date: 2015-07-29, Last modification date: 2023-09-20)

Primary citation

Wang, C.,Shen, M.,Gohain, N.,Tolbert, W.D.,Chen, F.,Zhang, N.,Yang, K.,Wang, A.,Su, Y.,Cheng, T.,Zhao, J.,Pazgier, M.,Wang, J.
Design of a potent antibiotic peptide based on the active region of human defensin 5.
J.Med.Chem., 58:3083-3093, 2015

PubMed Abstract: Human defensin 5 (HD5) is a broad-spectrum antibacterial peptide with a C-terminal active region. To promote the development of this peptide into an antibiotic, we initially substituted Glu21 with Arg because it is an electronegative residue located around the active region. Although detrimental to dimer formation, the E21R substitution markedly enhanced the antibacterial activity of HD5 and increased its ability to penetrate cell membranes, demonstrating that increasing the electropositive charge compensated for the effect of dimer disruption. Subsequently, a partial Arg scanning mutagenesis was performed, and Thr7 was selected for replacement with Arg to further strengthen the antibacterial activity. The newly designed peptide, T7E21R-HD5, exhibited potent antibacterial activity, even in saline and serum solutions. In contrast to monomeric E21R-HD5, T7E21R-HD5 assembled into an atypical dimer with parallel β strands, thus expanding the role of increasing electropositive charge in bactericidal activity and providing a useful guide for further defensin-derived antibiotic design.

PubMed: 25782105
DOI: 10.1021/jm501824a

Experimental method

X-RAY DIFFRACTION (1.5 Å)