6GR0

Petrobactin-binding engineered lipocalin in complex with gallium-petrobactin

6GR0 の概要

• エントリーDOI: 10.2210/pdb6gr0/pdb
• 分子名称: Neutrophil gelatinase-associated lipocalin, 4-[4-[3-[[3,4-bis(oxidanyl)phenyl]carbonylamino]propylamino]butylamino]-2-[2-[4-[3-[[3,4-bis(oxidanyl)phenyl]carbonylamino]propylamino]butylamino]-2-oxidanylidene-ethyl]-2-oxidanyl-4-oxidanylidene-butanoic acid, GALLIUM (III) ION, ... (4 entities in total)
• 機能のキーワード: anticalin, beta-barrel, petrobactin, lcn2, lipocalin, ngal, protein engineering, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 65202.57

構造登録者

Skerra, A.,Eichinger, A. (登録日: 2018-06-08, 公開日: 2018-08-15, 最終更新日: 2024-11-06)

主引用文献

Dauner, M.,Eichinger, A.,Lucking, G.,Scherer, S.,Skerra, A.
Reprogramming Human Siderocalin To Neutralize Petrobactin, the Essential Iron Scavenger of Anthrax Bacillus.
Angew. Chem. Int. Ed. Engl., 57:14619-14623, 2018

PubMed Abstract: Bacillus anthracis owes its pronounced virulence-apart from specific toxins-to a twofold import mechanism for Fe ions. This pathogenic bacterium secretes the siderophores bacillibactin (BB) and petrobactin (PB), of which only BB is neutralized by human siderocalin, an abundant lipocalin in plasma. We describe its reshaping via combinatorial protein design to bind PB⋅Fe instead of BB⋅Fe , and with even higher affinity (K ≈20 pm). X-ray crystallographic analysis of the resulting "petrocalin" in complex with PB⋅Ga reveals a positively charged ligand pocket while the extended butterfly-like conformation of the bound PB provides a rationale for the missing recognition by the natural siderocalin. In microbiological studies, a combination of petrocalin and siderocalin effectively suppressed the growth of a BB /PB strain of Bacillus cereus under iron-limiting culture conditions. Thus, our reprogrammed lipocalin may offer novel treatment options for devastating infections caused by B. anthracis.

PubMed: 30063283
DOI: 10.1002/anie.201807442

実験手法

X-RAY DIFFRACTION (2.5 Å)