Document Detail

Evolutionary analysis of the TPP-dependent enzyme family.
MedLine Citation:
PMID:  18043855     Owner:  NLM     Status:  MEDLINE    
The evolutionary relationships of the thiamine pyrophosphate (TPP)-dependent family of enzymes was investigated by generation of a neighbor joining phylogenetic tree using sequences from the conserved pyrophosphate (PP) and pyrimidine (Pyr) binding domains of 17 TPP-dependent enzymes. This represents the most comprehensive analysis of TPP-dependent enzyme evolution to date. The phylogeny was shown to be robust by comparison with maximum likelihood trees generated for each individual enzyme and also broadly confirms the evolutionary history proposed recently from structural comparisons alone (Duggleby 2006). The phylogeny is most parsimonious with the TPP enzymes having arisen from a homotetramer which subsequently diverged into an alpha(2)beta(2) heterotetramer. The relationship between the PP- and Pyr-domains and the recruitment of additional protein domains was examined using the transketolase C-terminal (TKC)-domain as an example. This domain has been recruited by several members of the family and yet forms no part of the active site and has unknown function. Removal of the TKC-domain was found to increase activity toward beta-hydroxypyruvate and glycolaldehyde. Further truncations of the Pyr-domain yielded several variants with retained activity. This suggests that the influence of TKC-domain recruitment on the evolution of the mechanism and specificity of transketolase (TK) has been minor, and that the smallest functioning unit of TK comprises the PP- and Pyr-domains, whose evolutionary histories extend to all TPP-dependent enzymes.
Seán J Costelloe; John M Ward; Paul A Dalby
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Publication Detail:
Type:  Journal Article     Date:  2007-11-28
Journal Detail:
Title:  Journal of molecular evolution     Volume:  66     ISSN:  0022-2844     ISO Abbreviation:  J. Mol. Evol.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-24     Completed Date:  2008-04-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0360051     Medline TA:  J Mol Evol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  36-49     Citation Subset:  IM    
Department of Biochemical Engineering, University College London, Torrington Place, London, UK.
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MeSH Terms
Amino Acid Sequence
Conserved Sequence
Enzymes / chemistry*,  classification*,  genetics
Models, Molecular
Protein Structure, Tertiary
Sequence Deletion
Sequence Homology, Amino Acid
Structural Homology, Protein
Thiamine Pyrophosphate / metabolism*
Transketolase / chemistry,  classification,  genetics
Reg. No./Substance:
0/Enzymes; 154-87-0/Thiamine Pyrophosphate; EC

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