Document Detail


Origin and evolution of peptide-modifying dioxygenases and identification of the wybutosine hydroxylase/hydroperoxidase.
MedLine Citation:
PMID:  20423905     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Unlike classical 2-oxoglutarate and iron-dependent dioxygenases, which include several nucleic acid modifiers, the structurally similar jumonji-related dioxygenase superfamily was only known to catalyze peptide modifications. Using comparative genomics methods, we predict that a family of jumonji-related enzymes catalyzes wybutosine hydroxylation/peroxidation at position 37 of eukaryotic tRNAPhe. Identification of this enzyme raised questions regarding the emergence of protein- and nucleic acid-modifying activities among jumonji-related domains. We addressed these with a natural classification of DSBH domains and reconstructed the precursor of the dioxygenases as a sugar-binding domain. This precursor gave rise to sugar epimerases and metal-binding sugar isomerases. The sugar isomerase active site was exapted for catalysis of oxygenation, with a radiation of these enzymes in bacteria, probably due to impetus from the primary oxygenation event in Earth's history. 2-Oxoglutarate-dependent versions appear to have further expanded with rise of the tricarboxylic acid cycle. We identify previously under-appreciated aspects of their active site and multiple independent innovations of 2-oxoacid-binding basic residues among these superfamilies. We show that double-stranded β-helix dioxygenases diversified extensively in biosynthesis and modification of halogenated siderophores, antibiotics, peptide secondary metabolites and glycine-rich collagen-like proteins in bacteria. Jumonji-related domains diversified into three distinct lineages in bacterial secondary metabolism systems and these were precursors of the three major clades of eukaryotic enzymes. The specificity of wybutosine hydroxylase/peroxidase probably relates to the structural similarity of the modified moiety to the ancestral amino acid substrate of this superfamily.
Authors:
Lakshminarayan M Iyer; Saraswathi Abhiman; Robson F de Souza; L Aravind
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-04-27
Journal Detail:
Title:  Nucleic acids research     Volume:  38     ISSN:  1362-4962     ISO Abbreviation:  Nucleic Acids Res.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-13     Completed Date:  2010-10-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0411011     Medline TA:  Nucleic Acids Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  5261-79     Citation Subset:  IM    
Affiliation:
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Bacteria / enzymology
Catalytic Domain
Dioxygenases / chemistry*,  genetics,  metabolism
Eukaryota / enzymology
Evolution, Molecular*
Genes, Bacterial
Mixed Function Oxygenases / chemistry*,  metabolism
Molecular Sequence Data
Nucleosides / metabolism*
Peptides / metabolism
Peroxidases / chemistry*,  metabolism
Protein Folding
Protein Structure, Secondary
Protein Structure, Tertiary
RNA, Transfer, Phe / metabolism
Sequence Homology, Amino Acid
Chemical
Reg. No./Substance:
0/Nucleosides; 0/Peptides; 0/RNA, Transfer, Phe; 0/wybutosine; EC 1.-/Mixed Function Oxygenases; EC 1.11.1.-/Peroxidases; EC 1.13.11.-/Dioxygenases

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


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