1QKC

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

Summary for 1QKC

• Entry DOI: 10.2210/pdb1qkc/pdb
• Related: 1BY3 1BY5 1FCP 1QFF 1QFG 1QJQ 2FCP
• Descriptor: FERRIC HYDROXAMATE RECEPTOR, alpha-D-glucopyranose-(1-2)-alpha-D-glucopyranose-(1-3)-[alpha-D-galactopyranose-(1-6)]alpha-D-glucopyranose-(1-3)-[L-glycero-alpha-D-manno-heptopyranose-(1-7)]L-glycero-alpha-D-manno-heptopyranose-(1-3)-L-glycero-alpha-D-manno-heptopyranose-(1-5)-[3-deoxy-alpha-D-manno-oct-2-ulopyranosonic acid-(2-4)]3-deoxy-alpha-D-manno-oct-2-ulopyranosonic acid-(2-6)-2-amino-2,3-dideoxy-alpha-D-glucoyranose-(1-6)-2-amino-2-deoxy-alpha-D-glucopyranose, 3-HYDROXY-TETRADECANOIC ACID, ... (8 entities in total)
• Functional Keywords: tonb dependent receptor, tonb-dependent receptor, integral outer membrane protein, ferrichrome, siderophore receptor, antibiotic, albomycin, active transporter, iron transport protein
• Biological source: Escherichia coli K-12
• Total number of polymer chains: 1
• Total formula weight: 85149.42

Authors

Ferguson, A.D.,Braun, V.,Fiedler, H.-P.,Coulton, J.W.,Diederichs, K.,Welte, W. (deposition date: 1999-07-18, release date: 2000-06-05, Last modification date: 2024-10-23)

Primary citation

Ferguson, A.D.,Braun, V.,Fiedler, H.P.,Coulton, J.W.,Diederichs, K.,Welte, W.
Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuA.
Protein Sci., 9:956-963, 2000

PubMed Abstract: 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.

PubMed: 10850805
DOI: 10.1110/ps.9.5.956

Experimental method

X-RAY DIFFRACTION (3.1 Å)