Linked Life Data

9878449

Source:http://linkedlifedata.com/resource/pubmed/id/9878449

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-3-11
pubmed:abstractText
A remarkable conformational rearrangement occurs upon Ca2+/Mg2+ exchange in the C-terminal EF-hand site (labelled site EF or EF-4) of parvalbumin, as initially established by X-ray crystallography. Such a conformational rearrangement is characterised as follows: (i) the co-ordination number decreases from seven oxygen atoms in the Ca-loaded form to six oxygen atoms in the Mg-loaded form, the heptaco-ordination of Ca2+ corresponding with a skewed pentagonal bipyramid configuration of the seven oxygen atoms, whereas the hexaco-ordination of Mg2+ corresponds with a regular octahedral configuration of the six oxygen atoms; and (ii) Glu101, at the relative position 12 in the EF-hand loop sequence (labelled "Glu12"), acts as a bidentate ligand in the Ca-loaded form and as a monodentate ligand in the Mg-loaded form. As part of the conformational rearrangement, the chi1 dihedral angle undergoes a gauche(+) to gauche(-) transition upon substitution of Ca2+ by Mg2+, whereas the chi2 angle remains practically unchanged and the chi3 angles in both forms adopt a nearly mirror image relationship. In order to understand the molecular mechanisms underlying such a conformational rearrangement, we undertook a theoretical study using the free energy perturbation (FEP) method, starting from high-resolution crystal structures of the same parvalbumin (pike 4. 10 isoform) differing by the substitution of their two cationic sites EF-3 (or CD) and EF-4 (or EF), i.e. the 1pal structure with EF-3(Ca2+) and EF-4(Ca2+), the 4pal structure with EF-3(Ca2+) and EF-4(Mg2+). When Mg2+ is "alchemically" transformed into Ca2+ within the EF-4 site of 4pal, the conformational rearrangement of Glu12 is correctly predicted by the FEP calculation. When Ca2+ is transformed into Mg2+ within the EF-3 site of 4pal, the FEP calculation predicts the topology of the fully Mg-loaded form for which no crystallographic data is presently available. As expected, Glu62 (at the relative position 12 in EF-3 loop) is predicted to be a monodentate residue within a regular octahedral arrangement of six oxygen atoms around Mg2+. We also investigated the behaviour during Ca2+/Mg2+ exchange of two other typical EF-hand proteins, troponin C (TnC) and calmodulin (CaM), for which no three-dimensional structure of their Mg-loaded forms is available so far. It is also predicted that the EF-3 site of TnC and the EF-1 site of CaM have their invariant Glu12 residues switching from the bidentate to the monodentate configuration when Ca2+ is substituted by Mg2+, with six oxygen atoms being observed in the co-ordination sphere of the alchemically generated Mg2+ cation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2836
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
857-73
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Ca2+/Mg2+ exchange in parvalbumin and other EF-hand proteins. A theoretical study.
pubmed:affiliation
Laboratoire de Physique Quantique, UMR 5626 of C.N.R.S., I.R.S.A.M.C., Université Paul Sabatier, 118 route de Narbonne, Toulouse Cédex, 31062, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't