Document Detail


Imposing function down a (cupin)-barrel: secondary structure and metal stereochemistry in the αKG-dependent oxygenases.
MedLine Citation:
PMID:  23446356     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Fe(ii)/αketoglutarate (αKG) dependent oxygenases catalyze a diverse range of reactions significant in biological processes such as antibiotic biosynthesis, lipid metabolism, oxygen sensing, and DNA and RNA repair. Although functionally diverse, the eight-stranded β-barrel (cupin) and HX(D/E)XnH facial triad motifs are conserved in this super-family of enzymes. Crystal structure analysis of 25 αKG oxygenases reveals two stereoisomers of the Fe cofactor, Anti and Clock, which differ in the relative position of the exchangeable ligand position and the primary substrate. Herein, we discuss the relationship between the chemical mechanism and the secondary coordination sphere of the αKG oxygenases, within the constraints of the stereochemistry of the Fe cofactor. Sequence analysis of the cupin barrel indicates that a small subset of positions constitute the second coordination sphere, which has significant ramifications for the structure of the ferryl intermediate. The competence of both Anti and Clock stereoisomers of Fe points to a ferryl intermediate that is 5 coordinate. The small number of conserved close contacts within the active sites of αKG oxygenases can be extended to chemically related enzymes, such as the αKG-dependent halogenases SyrB2 and CytC3, and the non-αKG dependent dioxygenases isopenicillin N synthase (IPNS) and cysteine dioxygenase (CDO).
Authors:
John A Hangasky; Cornelius Y Taabazuing; Meaghan A Valliere; Michael J Knapp
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Metallomics : integrated biometal science     Volume:  5     ISSN:  1756-591X     ISO Abbreviation:  Metallomics     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-28     Completed Date:  2013-09-17     Revised Date:  2014-08-03    
Medline Journal Info:
Nlm Unique ID:  101478346     Medline TA:  Metallomics     Country:  England    
Other Details:
Languages:  eng     Pagination:  287-301     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Ketoglutaric Acids
Metals / chemistry*,  metabolism
Molecular Sequence Data
Oxygenases / chemistry*,  metabolism*
Protein Structure, Secondary
Stereoisomerism
Substrate Specificity
Grant Support
ID/Acronym/Agency:
R01 GM077413/GM/NIGMS NIH HHS; T32 GM008515/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Ketoglutaric Acids; 0/Metals; 328-50-7/alpha-ketoglutaric acid; EC 1.13.-/Oxygenases
Comments/Corrections

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


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