Linked Life Data

16487591

Source:http://linkedlifedata.com/resource/pubmed/id/16487591

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5-6
pubmed:dateCreated
2006-5-8
pubmed:abstractText
The mechanisms by which metal ions are sensed in bacterial cells by metal-responsive transcriptional regulators (metal sensor proteins) may be strongly influenced by the kinetics of association and dissociation of specific metal ions with specific metalloregulatory targets. Staphylococcus aureus pI258-encoded CadC senses toxic metal pollutants such as Cd(II), Pb(II) and Bi(III) with very high thermodynamic affinities ( approximately 10(12)M(-1)) in forming either distorted tetrahedral (Cd/Bi) or trigonal (Pb) coordination complexes with cysteine thiolate ligands derived from the N-terminal domain (Cys7/11) and a pair of Cys in the alpha4 helix (Cys58/60). We show here that metal ion binding to this site (denoted the alpha3N or type 1 metal site) is characterized by two distinct kinetic phases, a fast bimolecular encounter phase and a slower intramolecular conformational transition. Metal association rates are fast ( approximately 10(5)-10(7)M(-1)s(-1)) and strongly dependent on the metal ion type in a manner that correlates with metal specificity in vivo. In contrast, the observed rate of the slower isomerization step is independent of the metal ion type (2.8+/-0.4s(-1)) but is reduced 6-fold upon substitution of Cys7, a key metal ligand that drives allosteric negative regulation of DNA binding. Chelator (EDTA)-mediated metal dissociation rates from the alpha3N site are extremely slow (10(-4)s(-1)). Where observable dissociation can be observed, a ternary CadC-metal ion-chelator complex is invoked, suggesting that metal-ligand exchange may be an important factor in metal sensing and resistance in the cell.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0162-0134
pubmed:author
pubmed:issnType
Print
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1024-34
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Kinetics of metal binding by the toxic metal-sensing transcriptional repressor Staphylococcus aureus pI258 CadC.
pubmed:affiliation
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-2128, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural