Document Detail


TrAnsFuSE refines the search for protein function: oxidoreductases.
MedLine Citation:
PMID:  22481248     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Non-equilibrium catalysis of electron transfer reactions (i.e. redox) regulates the flux of key elements found in biological macromolecules. The enzymes responsible, oxidoreductases, contain specific transition metals in poorly sequence-conserved domains. These domains evolved ∼2.4 billion years ago in microbes and spread across the tree of life. We lack understanding of how oxidoreductases evolved; divergence of sequences makes identification difficult. We developed a method to recognise the various versions of these enzyme-domains in unannotated sequence-space. Often, homology is used to transfer function annotations from experimentally resolved domains to unannotated sequences. Unreliability of inferring homology below 30% sequence identity limits single-sequence based searches. Misaligned functional sites may compromise annotation transfer from even very similar sequences. Combining profile-based searches with knowledge of functional sites could improve domain detection accuracy. Here we present an approach that enhances the search for redox domains using catalytic site annotations. From the scientific literature, we validated annotations of 104 InterPro domains indicated as using "transition metals in redox reactions." These domains mediate electron transfer in 20% of oxidoreductases, primarily employing iron, copper and molybdenum. We used the experimentally identified catalytic residues in these domains to validate sequence alignment-based protein function annotations. Our method, TrAnsFuSE, is 11% and 14% more accurate than PSI-BLAST and InterPro, respectively. Moreover, it is robust for use with other functional residues-we attain higher accuracy at comparable coverage using metal binding, in addition to catalytic, sites. TrAnsFuSE can be used to focus the study of the vast amounts of unannotated sequencing data from meta-/genome projects.
Authors:
Arye Harel; Paul Falkowski; Yana Bromberg
Related Documents :
9490068 - 4-hydroxybenzoyl-coa reductase (dehydroxylating) from the denitrifying bacterium thauer...
23405288 - Genome sequence of a novel archaeal rudivirus recovered from a mexican hot spring.
24929518 - Cloning of tae-mir156 precursor gene and sequence polymorphisms of tae-mir156 targeted ...
12450118 - Two genes encoding fruit body lectins of pleurotus cornucopiae: sequence similarity wit...
21305018 - Micrornas differentially expressed in postnatal aortic development downregulate elastin...
2045108 - Characterization and chromosomal mapping of a genomic clone encoding human alanine:glyo...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-5
Journal Detail:
Title:  Integrative biology : quantitative biosciences from nano to macro     Volume:  -     ISSN:  1757-9708     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101478378     Medline TA:  Integr Biol (Camb)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Environmental Biophysics and Molecular Ecology Program, Institute of Marine and Coastal Science, Rutgers the State University of New Jersey, 71 Dudley Road, New Brunswick, NJ 08901, USA. harel@marine.rutgers.edu.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

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


Previous Document:  Risky communication in atherosclerosis and thrombus formation.
Next Document:  Anomalous response of supported few-layer hexagonal boron nitride to DC electric fields: a confined ...