6GQZ

Petrobactin-binding engineered lipocalin without ligand

Summary for 6GQZ

• Entry DOI: 10.2210/pdb6gqz/pdb
• Descriptor: Neutrophil gelatinase-associated lipocalin (2 entities in total)
• Functional Keywords: anticalin, beta-barrel, petrobactin, lcn2, lipocalin, ngal, protein engineering, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 40267.83

Authors

Skerra, A.,Eichinger, A. (deposition date: 2018-06-08, release date: 2018-08-15, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.4 Å)