Linked Life Data

16499928

Source:http://linkedlifedata.com/resource/pubmed/id/16499928

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-3-27
pubmed:abstractText
Pyochelin (Pch) is a siderophore that is produced in iron-limited conditions, by both Pseudomonas aeruginosa and Burkholderia cepacia. This iron uptake pathway could therefore be a target for the development of new antibiotics. Pch is (4'R,2''R/S,4''R)-2'-(2-hydroxyphenyl)-3''-methyl-4',5',2'',3'',4'',5''-hexahydro-[4',2'']bithiazolyl-4''-carboxylic acid, and has three chiral centres located at positions C4', C2'' and C4''. In P.aeruginosa, this siderophore chelates iron in the extracellular medium and transports it into the cells via a specific outer membrane transporter FptA. Docking experiments using the X-ray structure of FptA-Pch-Fe showed that iron-loaded or unloaded Pch diastereoisomers could bind to FptA. This was confirmed by in vivo binding assays. These binding properties and the iron uptake ability were not affected by removal of the C4' chiral centre. After removal of both the C4' and C2'' chiral centres, the molecule still bound to FptA but was unable to transport iron. The overall binding mode of this iron-complexed analogue was inverted. These findings describe the first antagonist of the Pch/FptA iron uptake pathway. Pch also complexes with iron in conjunction with other bidentate ligands such as cepabactin (Cep) or ethylene glycol. Docking experiments showed that such complexes bind to FptA via the Pch molecule. The mixed Pch-Fe-Cep complex was also recognized by FptA, having an affinity intermediate between that for Pch(2)-Fe and Cep(3)-Fe. Finally, the iron uptake properties of the different Pch-related molecules suggested a mechanism for FptA-Pch-Fe complex formation similar to that of the FpvA/Pvd uptake system. All these findings improve our understanding of specificity of the interaction between FptA and its siderophore.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
357
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1437-48
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Binding properties of pyochelin and structurally related molecules to FptA of Pseudomonas aeruginosa.
pubmed:affiliation
Métaux et Microorganismes: Chimie, Biologie et Applications, UMR 7175-LC1 Institut Gilbert-Laustriat, CNRS, Université Louis Pasteur (Strasbourg 1), ESBS, Bld Sébastien Brant, F-67413 Illkirch, Strasbourg, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't