1qkc
From Proteopedia
(New page: 200px<br /><applet load="1qkc" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qkc, resolution 3.10Å" /> '''ESCHERICHIA COLI FER...) |
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| - | [[Image:1qkc.jpg|left|200px]]<br /><applet load="1qkc" size=" | + | [[Image:1qkc.jpg|left|200px]]<br /><applet load="1qkc" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1qkc, resolution 3.10Å" /> | caption="1qkc, resolution 3.10Å" /> | ||
'''ESCHERICHIA COLI FERRIC HYDROXAMATE UPTAKE RECEPTOR (FHUA) IN COMPLEX DELTA TWO-ALBOMYCIN'''<br /> | '''ESCHERICHIA COLI FERRIC HYDROXAMATE UPTAKE RECEPTOR (FHUA) IN COMPLEX DELTA TWO-ALBOMYCIN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | One alternative method for drug delivery involves the use of | + | 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== | ==About this Structure== | ||
| - | 1QKC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with PO4, NI, FTT, DPO and ALB as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1QKC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=NI:'>NI</scene>, <scene name='pdbligand=FTT:'>FTT</scene>, <scene name='pdbligand=DPO:'>DPO</scene> and <scene name='pdbligand=ALB:'>ALB</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QKC OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Braun, V.]] | [[Category: Braun, V.]] | ||
| - | [[Category: Coulton, J | + | [[Category: Coulton, J W.]] |
[[Category: Diederichs, K.]] | [[Category: Diederichs, K.]] | ||
| - | [[Category: Ferguson, A | + | [[Category: Ferguson, A D.]] |
| - | [[Category: Fiedler, H | + | [[Category: Fiedler, H P.]] |
[[Category: Welte, W.]] | [[Category: Welte, W.]] | ||
[[Category: ALB]] | [[Category: ALB]] | ||
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[[Category: tonb-dependent receptor]] | [[Category: tonb-dependent receptor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:40:37 2008'' |
Revision as of 12:40, 21 February 2008
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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 , , , and 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
Page seeded by OCA on Thu Feb 21 14:40:37 2008
Categories: Escherichia coli | Single protein | Braun, V. | Coulton, J W. | Diederichs, K. | Ferguson, A D. | Fiedler, H P. | Welte, W. | ALB | DPO | FTT | NI | PO4 | Active transporter | Albomycin | Antibiotic | Ferrichrome | Integral outer membrane protein | Iron transport protein | Siderophore receptor | Tonb-dependent receptor
