Document Detail


Quaternary protein modeling to predict the function of DNA variation found in human mitochondrial cytochrome c oxidase.
MedLine Citation:
PMID:  23303385     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cytochrome c oxidase (COX) of the electron transport system is thought to be the rate-limiting step in cellular respiration and is found mutated in numerous human pathologies. Here, we employ quaternary three-dimensional (3-D) modeling to construct a model for human COX. The model was used to predict the functional consequences of amino-acid mutations based on phylogenetic conservation of amino acids together with volume and/or steric perturbations, participation in subunit-subunit interfaces and non-covalent energy loss or incompatibilities. These metrics were combined and interpreted for potential functional impact. A notable strength of the 3-D model is that it can interpret and predict the structural consequences of amino-acid variation in all 13 protein subunits. Importantly, the influence of compensatory changes can also be modeled. We examine mutations listed in the human mutation database Mitomap, and in 100 older men, and compare the results from the 3-D model against the automated MutPred web application tool. In combination, these comparisons suggest that the 3-D model predicts more functionally significant mutations than does MutPred. We conclude that the model has useful functional prediction capability but may need modification as functional data on specific mutations becomes known.Journal of Human Genetics advance online publication, 10 January 2013; doi:10.1038/jhg.2012.144.
Authors:
Martin Patrick Horan; Jon N Rumbley; Richard G Melvin; David G Le Couteur; J William O Ballard
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-10
Journal Detail:
Title:  Journal of human genetics     Volume:  -     ISSN:  1435-232X     ISO Abbreviation:  J. Hum. Genet.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9808008     Medline TA:  J Hum Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
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