3LN2

Crystal Structure of a Charge Engineered Human Lysozyme Variant

3LN2 の概要

• エントリーDOI: 10.2210/pdb3ln2/pdb
• 分子名称: Lysozyme C (2 entities in total)
• 機能のキーワード: human lysozyme, hydrolase, charge engineered human lysozyme, protein engineering, antimicrobial, bacteriolytic, surface mutation, amyloid, amyloidosis, bacteriolytic enzyme, disease mutation, disulfide bond, glycosidase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P61626
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29319.08

構造登録者

Gill, A.,Scanlon, T.C.,Griswold, K.E. (登録日: 2010-02-01, 公開日: 2011-02-16, 最終更新日: 2024-10-16)

主引用文献

Gill, A.,Scanlon, T.C.,Osipovitch, D.C.,Madden, D.R.,Griswold, K.E.
Crystal structure of a charge engineered human lysozyme having enhanced bactericidal activity.
Plos One, 6:e16788-e16788, 2011

PubMed Abstract: Human lysozyme is a key component of the innate immune system, and recombinant forms of the enzyme represent promising leads in the search for therapeutic agents able to treat drug-resistant infections. The wild type protein, however, fails to participate effectively in clearance of certain infections due to inherent functional limitations. For example, wild type lysozymes are subject to electrostatic sequestration and inactivation by anionic biopolymers in the infected airway. A charge engineered variant of human lysozyme has recently been shown to possess improved antibacterial activity in the presence of disease associated inhibitory molecules. Here, the 2.04 Å crystal structure of this variant is presented along with an analysis that provides molecular level insights into the origins of the protein's enhanced performance. The charge engineered variant's two mutated amino acids exhibit stabilizing interactions with adjacent native residues, and from a global perspective, the mutations cause no gross structural perturbations or loss of stability. Importantly, the two substitutions dramatically expand the negative electrostatic potential that, in the wild type enzyme, is restricted to a small region near the catalytic residues. The net result is a reduction in the overall strength of the engineered enzyme's electrostatic potential field, and it appears that the specific nature of this remodeled field underlies the variant's reduced susceptibility to inhibition by anionic biopolymers.

PubMed: 21408218
DOI: 10.1371/journal.pone.0016788

実験手法

X-RAY DIFFRACTION (2.037 Å)