PDBsum entry 3h6c

Antimicrobial protein

PDB id: 3h6c

Contents

Protein chains

30 a.a. *

Ligands

PEG ×2

Metals

_CL ×3

Waters ×46

* Residue conservation analysis

PDB id:

3h6c

Name:

Antimicrobial protein

Title:

Crystal structure of human alpha-defensin 1 (mutant gln22ala)

Structure:

Neutrophil defensin 1. Chain: a, b. Synonym: hnp-1, hp-1, hp1, defensin, alpha 1, hp 1-56, neutrophil defensin 2, hnp-2, hp-2, hp2. Engineered: yes. Mutation: yes

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606

Resolution:

1.63Å R-factor: 0.185 R-free: 0.199

Authors:

M.Pazgier,W.Lu

Key ref:

G.Wei et al. (2010). Trp-26 imparts functional versatility to human alpha-defensin HNP1. J Biol Chem, 285, 16275-16285. PubMed id: 20220136

Date:

23-Apr-09 Release date: 09-Mar-10

Protein chains

P59665  (DEF1_HUMAN) -  Neutrophil defensin 1 from Homo sapiens

Seq: 94 a.a.

Struc: 30 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

J Biol Chem 285:16275-16285 (2010)

PubMed id: 20220136

Trp-26 imparts functional versatility to human alpha-defensin HNP1.

G.Wei, M.Pazgier, E.de Leeuw, M.Rajabi, J.Li, G.Zou, G.Jung, W.Yuan, W.Y.Lu, R.I.Lehrer, W.Lu.

ABSTRACT

We performed a comprehensive alanine scan of human alpha-defensin HNP1 and tested the ability of the resulting analogs to kill Staphylococcus aureus, inhibit anthrax lethal factor, and bind human immunodeficiency virus-1 gp120. By far, the most deleterious mutation for all of these functions was W26A. The activities lost by W26A-HNP1 were restored progressively by replacing W26 with non-coded, straight-chain aliphatic amino acids of increasing chain length. The hydrophobicity of residue 26 also correlated with the ability of the analogs to bind immobilized wild type HNP1 and to undergo further self-association. Thus, the hydrophobicity of residue 26 is not only a key determinant of the direct interactions of HNP1 with target molecules, but it also governs the ability of this peptide to form dimers and more complex quaternary structures at micromolar concentrations. Although all defensin peptides are cationic, their amphipathicity is at least as important as their positive charge in enabling them to participate in innate host defense.