1k2v: Difference between revisions
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==E. COLI PERIPLASMIC PROTEIN FHUD COMPLEXED WITH DESFERAL== | |||
<StructureSection load='1k2v' size='340' side='right'caption='[[1k2v]], [[Resolution|resolution]] 1.97Å' scene=''> | |||
| | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1k2v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K2V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1K2V FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.97Å</td></tr> | |||
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DEF:DEFEROXAMINE+MESYLATE+FE(III)+COMPLEX'>DEF</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1k2v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k2v OCA], [https://pdbe.org/1k2v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1k2v RCSB], [https://www.ebi.ac.uk/pdbsum/1k2v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1k2v ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FHUD_ECOLI FHUD_ECOLI] Part of the ABC transporter complex FhuCDB involved in iron(3+)-hydroxamate import. Binds the iron(3+)-hydroxamate complex and transfers it to the membrane-bound permease. Required for the transport of all iron(3+)-hydroxamate siderophores such as ferrichrome, gallichrome, desferrioxamine, coprogen, aerobactin, shizokinen, rhodotorulic acid and the antibiotic albomycin. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k2/1k2v_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1k2v ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Siderophore-binding proteins play an essential role in the uptake of iron in many Gram-positive and Gram-negative bacteria. FhuD is an ATP-binding cassette-type (ABC-type) binding protein involved in the uptake of hydroxamate-type siderophores in Escherichia coli. Structures of FhuD complexed with the antibiotic albomycin, the fungal siderophore coprogen and the drug Desferal have been determined at high resolution by x-ray crystallography. FhuD has an unusual bilobal structure for a periplasmic ligand binding protein, with two mixed beta/alpha domains connected by a long alpha-helix. The binding site for hydroxamate-type ligands is composed of a shallow pocket that lies between these two domains. Recognition of siderophores primarily occurs through interactions between the iron-hydroxamate centers of each siderophore and the side chains of several key residues in the binding pocket. Rearrangements of side chains within the binding pocket accommodate the unique structural features of each siderophore. The backbones of the siderophores are not involved in any direct interactions with the protein, demonstrating how siderophores with considerable chemical and structural diversity can be bound by FhuD. For albomycin, which consists of an antibiotic group attached to a hydroxamate siderophore, electron density for the antibiotic portion was not observed. Therefore, this study provides a basis for the rational design of novel bacteriostatic agents, in the form of siderophore-antibiotic conjugates that can act as "Trojan horses," using the hydroxamate-type siderophore uptake system to actively deliver antibiotics directly into targeted pathogens. | |||
X-ray crystallographic structures of the Escherichia coli periplasmic protein FhuD bound to hydroxamate-type siderophores and the antibiotic albomycin.,Clarke TE, Braun V, Winkelmann G, Tari LW, Vogel HJ J Biol Chem. 2002 Apr 19;277(16):13966-72. Epub 2002 Jan 22. PMID:11805094<ref>PMID:11805094</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1k2v" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Ferric hydroxamate uptake receptor|Ferric hydroxamate uptake receptor]] | |||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Braun | [[Category: Braun V]] | ||
[[Category: Clarke | [[Category: Clarke TE]] | ||
[[Category: Tari | [[Category: Tari LW]] | ||
[[Category: Vogel | [[Category: Vogel HJ]] | ||
[[Category: Winkelmann | [[Category: Winkelmann G]] | ||
Latest revision as of 11:49, 16 August 2023
E. COLI PERIPLASMIC PROTEIN FHUD COMPLEXED WITH DESFERALE. COLI PERIPLASMIC PROTEIN FHUD COMPLEXED WITH DESFERAL
Structural highlights
FunctionFHUD_ECOLI Part of the ABC transporter complex FhuCDB involved in iron(3+)-hydroxamate import. Binds the iron(3+)-hydroxamate complex and transfers it to the membrane-bound permease. Required for the transport of all iron(3+)-hydroxamate siderophores such as ferrichrome, gallichrome, desferrioxamine, coprogen, aerobactin, shizokinen, rhodotorulic acid and the antibiotic albomycin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSiderophore-binding proteins play an essential role in the uptake of iron in many Gram-positive and Gram-negative bacteria. FhuD is an ATP-binding cassette-type (ABC-type) binding protein involved in the uptake of hydroxamate-type siderophores in Escherichia coli. Structures of FhuD complexed with the antibiotic albomycin, the fungal siderophore coprogen and the drug Desferal have been determined at high resolution by x-ray crystallography. FhuD has an unusual bilobal structure for a periplasmic ligand binding protein, with two mixed beta/alpha domains connected by a long alpha-helix. The binding site for hydroxamate-type ligands is composed of a shallow pocket that lies between these two domains. Recognition of siderophores primarily occurs through interactions between the iron-hydroxamate centers of each siderophore and the side chains of several key residues in the binding pocket. Rearrangements of side chains within the binding pocket accommodate the unique structural features of each siderophore. The backbones of the siderophores are not involved in any direct interactions with the protein, demonstrating how siderophores with considerable chemical and structural diversity can be bound by FhuD. For albomycin, which consists of an antibiotic group attached to a hydroxamate siderophore, electron density for the antibiotic portion was not observed. Therefore, this study provides a basis for the rational design of novel bacteriostatic agents, in the form of siderophore-antibiotic conjugates that can act as "Trojan horses," using the hydroxamate-type siderophore uptake system to actively deliver antibiotics directly into targeted pathogens. X-ray crystallographic structures of the Escherichia coli periplasmic protein FhuD bound to hydroxamate-type siderophores and the antibiotic albomycin.,Clarke TE, Braun V, Winkelmann G, Tari LW, Vogel HJ J Biol Chem. 2002 Apr 19;277(16):13966-72. Epub 2002 Jan 22. PMID:11805094[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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