1qkc

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spinqualitylabelsall models 1qkc, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

ESCHERICHIA COLI FERRIC HYDROXAMATE UPTAKE RECEPTOR (FHUA) IN COMPLEX DELTA TWO-ALBOMYCIN

Overview

One alternative method for drug delivery involves the use of, siderophore-antibiotic conjugates. These compounds represent a specific, means by which potent antimicrobial agents, covalently linked to, iron-chelating siderophores, can be actively transported across the outer, membrane of gram-negative bacteria. These "Trojan Horse" antibiotics may, prove useful as an efficient means to combat multi-drug-resistant, bacterial infections. Here we present the crystallographic structures of, the natural siderophore-antibiotic conjugate albomycin and the siderophore, phenylferricrocin, in complex with the active outer membrane transporter, FhuA from Escherichia coli. To our knowledge, this represents the first, structure of an antibiotic bound to its cognate transporter. Albomycins, are broad-host range antibiotics that consist of a hydroxamate-type, iron-chelating siderophore, and an antibiotically active, thioribosyl, pyrimidine moiety. As observed with other hydroxamate-type siderophores, the three-dimensional structure of albomycin reveals an identical, coordination geometry surrounding the ferric iron atom. Unexpectedly, this, antibiotic assumes two conformational isomers in the binding site of FhuA, an extended and a compact form. The structural information derived from, this study provides novel insights into the diverse array of antibiotic, moieties that can be linked to the distal portion of iron-chelating, siderophores and offers a structural platform for the rational design of, hydroxamate-type siderophore-antibiotic conjugates.

About this Structure

1QKC is a Single protein structure of sequence from Escherichia coli with PO4, NI, FTT, DPO and ALB as ligands. Full crystallographic information is available from OCA.

Reference

Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuA., Ferguson AD, Braun V, Fiedler HP, Coulton JW, Diederichs K, Welte W, Protein Sci. 2000 May;9(5):956-63. PMID:10850805

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