Linked Life Data

18039668

Source:http://linkedlifedata.com/resource/pubmed/id/18039668

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-1-21
pubmed:abstractText
In the heme-based sensor Dos from Escherichia coli, the ferrous heme is coordinated by His-77 and Met-95. The latter residue is replaced upon oxygen binding or oxidation of the heme. Here we investigate the early signaling processes upon dissociation of the distal ligand using ultrafast spectroscopy and site-directed mutagenesis. Geminate CO rebinding to the heme domain DosH appears insensitive to replacement of Met-95, in agreement with the notion that this residue is oriented out of the heme pocket in the presence of external ligands. A uniquely slow 35-ps phase in rebinding of the flexible methionine side chain after dissociation from ferrous DosH is completely abolished in rebinding of the more rigid histidine side chain in the M95H mutant protein, where only the 7-ps phase, common to all 6-coordinate heme proteins, is observed. Temperature-dependence studies indicate that all rebinding of internal and external ligands is essentially barrierless, but that CfigsO escape from the heme pocket is an activated process. Solvent viscosity studies combined with molecular dynamics simulations show that there are two configurations in the ferrous 6-coordinate protein, involving two isomers of the Met-95 side chain, of which the structural changes extend to the solvent-exposed backbone, which is part of the flexible FG loop. One of these configurations has considerable motional freedom in the Met-95-dissociated state. We suggest that this configuration corresponds to an early signaling intermediate state, is responsible for the slow rebinding, and allows small ligands in the protein to efficiently compete for binding with the heme.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2344-52
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Ligand dynamics and early signaling events in the heme domain of the sensor protein Dos from Escherichia coli.
pubmed:affiliation
Laboratoire d'Optique et Biosciences, CNRS, Ecole Polytechnique, F-91128 Palaiseau and INSERM U696, F-91128 Palaiseau, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't