| Cyanide and nitric oxide binding to reduced protocatechuate 3,4-dioxygenase: insight into the basis for order-dependent ligand binding by intradiol catecholic dioxygenases. | |
| | |
MedLine Citation:
|
PMID: 9369476 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
EPR-silent, chemically reduced protocatechuate 3,4-dioxygenase (Er) binds NO at the active site Fe2+ to yield an EPR-active, S = 3/2 species that blocks subsequent binding of all other exogenous ligands. In contrast, addition of NO to a preformed Er.CN- complex yields an EPR-active, S = 1/2 species [Er.(CN)x.NO] that exhibits resolved superhyperfine splitting from 13CN-, 15/14NO, and a protein-derived 14N. Simulations of the EPR spectra observed for the Er.(CN)x.NO complex formed with 12CN- and 13CN- (1:1) show that CN- binds in two iron ligand sites (x >/= 2). The two cyanides exhibit similar, but distinguishable, hyperfine coupling constants. This demonstrates unambiguously that at least three exogenous ligands (two cyanides and NO) can bind to the Fe2+ simultaneously and strongly suggests that at least one histidine ligand is retained in the complex. The Er.(CN)>/=2.NO complex readily exchanges both of the bound cyanides for the substrate analog, 2-hydroxyisonicotinic acid N-oxide (INO), to form a Er.INO.NO complex exhibiting the same S = 3/2 type EPR spectrum that is observed for this complex in the absence of CN-. Because the dead-end Er.NO complex does not accumulate during the exchange, the results suggest that Er.(CN)>/=2. NO and Er.INO.NO are in conformational states that allow facile exchange of INO and CN- but not NO. The results are interpreted in the context of the known X-ray crystal structures for the ferric form of the resting enzyme (Eox) and numerous Eox.substrate, inhibitor, and CN- complexes, all of which have a charge neutral iron center. It is proposed that the binding of one CN- causes dissociation of an anionic endogenous ligand which begins a series of conformational changes analogous to those initiated by anionic substrate binding to Eox. This results in a new unique coordination site for NO, and a new second site for CN-; both cyanide sites are utilized when the enzyme subsequently binds substrates or INO. |
| | |
Authors:
|
A M Orville; J D Lipscomb |
Related Documents
:
|
1397976 - Estrogen binding sites in peripheral blood monocytes and effects of danazol on their si... 21038436 - Role of pocket flexibility in the modulation of estrogen receptor alpha by key residue ... 6548626 - A diphenylmethane derivative selective for the anti-estrogen binding site may help defi... 8647856 - Regulation of avian osteoclastic h+ -atpase and bone resorption by tamoxifen and calmod... 7512176 - Epitope tagging of dab389il-2: new insights into c-domain delivery to the cytosol of ta... 12526776 - Sr2+ binding to the ca2+ binding site of the synaptotagmin 1 c2b domain triggers fast e... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Biochemistry Volume: 36 ISSN: 0006-2960 ISO Abbreviation: Biochemistry Publication Date: 1997 Nov |
Date Detail:
|
Created Date: 1997-12-19 Completed Date: 1997-12-19 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 14044-55 Citation Subset: IM |
Affiliation:
|
Department of Biochemistry, Medical School, and Center for Metals in Biocatalysis, University of Minnesota, Minneapolis, Minnesota 55455-0347, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Cyanides
/
chemistry,
metabolism* Electron Spin Resonance Spectroscopy Iron Ligands Models, Chemical Nitric Oxide / chemistry, metabolism* Oxidation-Reduction Protocatechuate-3,4-Dioxygenase / chemistry, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
GM 24689/GM/NIGMS NIH HHS; GM-07323/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Cyanides; 0/Ligands; 10102-43-9/Nitric Oxide; 7439-89-6/Iron; EC 1.13.11.3/Protocatechuate-3,4-Dioxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Alanine scanning mutagenesis of the switch I region in the ATPase site of Dictyostelium discoideum m...
Next Document: RNA dependent DNA replication fidelity of HIV-1 reverse transcriptase: evidence of discrimination be...