| Ferritin reactions: direct identification of the site for the diferric peroxide reaction intermediate. | |
| | |
MedLine Citation:
|
PMID: 15166287 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Ferritins managing iron-oxygen biochemistry in animals, plants, and microorganisms belong to the diiron carboxylate protein family and concentrate iron as ferric oxide approximately 10(14) times above the ferric K(s). Ferritin iron (up to 4,500 atoms), used for iron cofactors and heme, or to trap DNA-damaging oxidants in microorganisms, is concentrated in the protein nanocage cavity (5-8 nm) formed during assembly of polypeptide subunits, 24 in maxiferritins and 12 in miniferritins/DNA protection during starvation proteins. Direct identification of ferritin ferroxidase (F(ox)) sites, complicated by multiple types of iron-ferritin interactions, is now achieved with chimeric proteins where putative F(ox) site residues were introduced singly and cumulatively into an inactive host, an L maxiferritin. A dimagnesium ferritin cocrystal model guided site design and the diferric peroxo F(ox) intermediates (A at 650 nm) monitored activity. Diferric peroxo formation in chimeric and WT proteins had similar K(app) values and Hill coefficients. Catalytic activity required cooperative ferrous substrate binding to two sites A (E, EXXH) and B (E, QXXD). The weaker B sites in ferritin contrast with stronger B sites (E, EXXH) in diiron carboxylate oxygenases, explaining diferric oxo/hydroxo product release in ferritin vs. diiron cofactor retention in oxygenases. Codons for Q/H and D/E differ by single nucleotides, suggesting simple DNA mutations relate site B diiron substrate sites and diiron cofactor sites in proteins. The smaller k(cat) values in chimeras indicate the absence of second-shell residues important for ferritin substrate-product channeling that, when identified, will outline the entire iron path from ferritin pores through the F(ox) site to the mineral cavity. |
| | |
Authors:
|
Xiaofeng Liu; Elizabeth C Theil |
Related Documents
:
|
10678937 - Iron acquisition from pseudomonas aeruginosa siderophores by human phagocytes: an addit... 9383187 - Energy-dependent changes in the gonococcal transferrin receptor. 6088317 - Iron uptake from sialo transferrins by rat reticulocytes. 8753797 - Specific orientation of porphyrin at the binding site of catalytic antibody. 3196027 - Influence of the guanine nucleotide phosphorylation state and of mg2+ ions on the inter... 12388737 - The human cytomegalovirus us10 gene product delays trafficking of major histocompatibil... |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2004-05-27 |
Journal Detail:
|
Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 101 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2004 Jun |
Date Detail:
|
Created Date: 2004-06-09 Completed Date: 2004-08-17 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
|
Languages: eng Pagination: 8557-62 Citation Subset: IM |
Affiliation:
|
Center for BioIron at Children's Hospital Oakland Research Institute, 5700 Martin Luther King Way, Oakland, CA 94609, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Sequence Animals Base Sequence Binding Sites DNA / genetics Ferritins / chemistry*, genetics, metabolism* Humans Hydrogen-Ion Concentration Kinetics Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Peroxides / chemistry, metabolism Recombinant Fusion Proteins / chemistry, genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
DK20251/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Peroxides; 0/Recombinant Fusion Proteins; 9007-49-2/DNA; 9007-73-2/Ferritins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Atypical haemolytic uraemic syndrome as a complication of induction chemotherapy for acute lymphobla...
Next Document: Plasmodium falciparum cysteine protease falcipain-1 is not essential in erythrocytic stage malaria p...