Document Detail

Effector role reversal during evolution: the case of frataxin in Fe-S cluster biosynthesis.
MedLine Citation:
PMID:  22352884     Owner:  NLM     Status:  MEDLINE    
Human frataxin (FXN) has been intensively studied since the discovery that the FXN gene is associated with the neurodegenerative disease Friedreich's ataxia. Human FXN is a component of the NFS1-ISD11-ISCU2-FXN (SDUF) core Fe-S assembly complex and activates the cysteine desulfurase and Fe-S cluster biosynthesis reactions. In contrast, the Escherichia coli FXN homologue CyaY inhibits Fe-S cluster biosynthesis. To resolve this discrepancy, enzyme kinetic experiments were performed for the human and E. coli systems in which analogous cysteine desulfurase, Fe-S assembly scaffold, and frataxin components were interchanged. Surprisingly, our results reveal that activation or inhibition by the frataxin homologue is determined by which cysteine desulfurase is present and not by the identity of the frataxin homologue. These data are consistent with a model in which the frataxin-less Fe-S assembly complex exists as a mixture of functional and nonfunctional states, which are stabilized by binding of frataxin homologues. Intriguingly, this appears to be an unusual example in which modifications to an enzyme during evolution inverts or reverses the mode of control imparted by a regulatory molecule.
Jennifer Bridwell-Rabb; Clara Iannuzzi; Annalisa Pastore; David P Barondeau
Related Documents :
11337984 - Purification and characterization of an extracellular lipase from penicillium candidum.
9470414 - Extracellular enzyme activities of dermatophytes and yeast isolates on solid media.
17325444 - Studies on the enhanced production of extracellular lipase by staphylococcus epidermidis.
18809324 - Membrane-bound 'synthetic lipase' specifically cultured under solid-state fermentation ...
228044 - Uncapping of viral messenger rna by phosphodiesterase of fibroblast plasma membranes.
12429124 - Presence of chitinase and beta-n-acetylglucosaminidase in the aedes aegypti. a chitinol...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-15
Journal Detail:
Title:  Biochemistry     Volume:  51     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-27     Completed Date:  2012-05-14     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2506-14     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Carbon-Sulfur Lyases / metabolism
Escherichia coli
Escherichia coli Proteins / metabolism
Iron / metabolism*
Iron-Binding Proteins / chemistry,  metabolism*
Iron-Regulatory Proteins / metabolism
Iron-Sulfur Proteins / metabolism
Sequence Homology, Amino Acid
Sulfur / metabolism*
Grant Support
1R01GM096100/GM/NIGMS NIH HHS; MC_U117584256//Medical Research Council; R01 GM096100-01A1/GM/NIGMS NIH HHS; U117584256//Medical Research Council
Reg. No./Substance:
0/CyaY protein, E coli; 0/Escherichia coli Proteins; 0/ISD11 protein, human; 0/Iron-Binding Proteins; 0/Iron-Regulatory Proteins; 0/Iron-Sulfur Proteins; 0/IscU protein, E coli; 0/frataxin; 70FD1KFU70/Sulfur; E1UOL152H7/Iron; EC 4.4.-/Carbon-Sulfur Lyases; EC 4.4.1.-/NFS1 protein, human; EC 4.4.1.-/cysteine desulfurase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Persistence with nebivolol in the treatment of hypertension: a retrospective claims analysis.
Next Document:  Long-term disease history, clinical symptoms, health status, and healthcare utilization in patients ...