Linked Life Data

12044175

Source:http://linkedlifedata.com/resource/pubmed/id/12044175

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2002-6-4
pubmed:abstractText
A defining feature of all transferrins is the absolute dependence of iron binding on the concomitant binding of a synergistic anion, normally but not necessarily carbonate. Acting as a bridging ligand between iron and protein, it completes the coordination requirements of iron to lock the essential metal in its binding site. To investigate the role of the synergistic anion in the iron-binding and iron-donating properties of human transferrin, a bilobal protein with an iron binding site in each lobe, we have selectively mutated the anion-binding threonine and arginine ligands that form an essential part of the electrostatic and hydrogen-bonding network holding the synergistic anion to the protein. Preservation of either ligand is sufficient to maintain anion binding, and therefore iron binding, in the mutated lobe. Arginine is a stronger ligand than threonine, and its loss weakens carbonate and therefore iron binding, but maintains the ability of nitrilotriacetate to serve as a carbonate surrogate. Replacement of both ligands abolishes anion binding and consequently iron binding in the affected lobe. Loss of anion binding in either lobe results in a monoferric protein binding iron in normal fashion only in the opposite lobe. Both monoferric proteins are capable of transferrin receptor-dependent binding and iron donation to K562 cells, but with diminished receptor occupancy by the protein bearing iron only in the N-lobe.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7416-23
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:12044175-Alanine, pubmed-meshheading:12044175-Anions, pubmed-meshheading:12044175-Arginine, pubmed-meshheading:12044175-Binding Sites, pubmed-meshheading:12044175-Carbonic Acid, pubmed-meshheading:12044175-Drug Synergism, pubmed-meshheading:12044175-Electron Spin Resonance Spectroscopy, pubmed-meshheading:12044175-Humans, pubmed-meshheading:12044175-Iron, pubmed-meshheading:12044175-K562 Cells, pubmed-meshheading:12044175-Kinetics, pubmed-meshheading:12044175-Mutagenesis, Site-Directed, pubmed-meshheading:12044175-Nitrilotriacetic Acid, pubmed-meshheading:12044175-Peptide Fragments, pubmed-meshheading:12044175-Recombinant Proteins, pubmed-meshheading:12044175-Serine, pubmed-meshheading:12044175-Spectrophotometry, pubmed-meshheading:12044175-Threonine, pubmed-meshheading:12044175-Transferrin
pubmed:year
2002
pubmed:articleTitle
The synergistic anion-binding sites of human transferrin: chemical and physiological effects of site-directed mutagenesis.
pubmed:affiliation
Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.