The Thiamine diphosphate dependent Enzyme Engineering Database: a tool for the systematic analysis of sequence and structure relations.

Michael Widmann,Jürgen Pleiss,Robert Radloff

doi:10.1186/1471-2091-11-9

Abstract

BackgroundThiamine diphosphate (ThDP)-dependent enzymes form a vast and diverse class of proteins, catalyzing a wide variety of enzymatic reactions including the formation or cleavage of carbon-sulfur, carbon-oxygen, carbon-nitrogen, and especially carbon-carbon bonds. Although very diverse in sequence and domain organisation, they share two common protein domains, the pyrophosphate (PP) and the pyrimidine (PYR) domain. For the comprehensive and systematic comparison of protein sequences and structures the Thiamine diphosphate (ThDP)-dependent Enzyme Engineering Database (TEED) was established.DescriptionThe TEED http://www.teed.uni-stuttgart.de contains 12048 sequence entries which were assigned to 9443 different proteins and 379 structure entries. Proteins were assigned to 8 different superfamilies and 63 homologous protein families. For each family, the TEED offers multisequence alignments, phylogenetic trees, and family-specific HMM profiles. The conserved pyrophosphate (PP) and pyrimidine (PYR) domains have been annotated, which allows the analysis of sequence similarities for a broad variety of proteins. Human ThDP-dependent enzymes are known to be involved in many diseases. 20 different proteins and over 40 single nucleotide polymorphisms (SNPs) of human ThDP-dependent enzymes were identified in the TEED.ConclusionsThe online accessible version of the TEED has been designed to serve as a navigation and analysis tool for the large and diverse family of ThDP-dependent enzymes.

Highlights

Thiamine diphosphate (ThDP)-dependent enzymes form a vast and diverse class of proteins, catalyzing a wide variety of enzymatic reactions including the formation or cleavage of carbon-sulfur, carbonoxygen, carbon-nitrogen, and especially carbon-carbon bonds
The online accessible version of the Thiamine diphosphate dependent Enzyme Engineering Database (TEED) has been designed to serve as a navigation and analysis tool for the large and diverse family of ThDP-dependent enzymes
ThDP-dependent enzymes catalyze a wide variety of enzymatic reactions and were assigned to the families of oxidoreductases, transferases, or lyases [4]

Summary

Background

Since the discovery of the first thiamine diphosphate (ThDP)-dependent enzyme in 1937, a multitude of them has been described and their catalytic mechanism was intensively analysed [1,2,3]. We established the Thiamine diphosphate dependent Enzyme Engineering Database (TEED) as a tool for a comprehensive and systematic comparison of ThDPdependent enzymes from different protein families and annotated the conserved PP- and PYR domains. The TEED is the first data resource of ThDP-dependent enzymes which combines information on the individual protein families, sequence alignments and a consistent annotation of the conserved PYR and PP domains. If no structure information was available, a set of sequences from the respective homologous protein family was selected and used to create a multisequence alignment. A reliable alignment was ensured by performing this analysis for each homologous family separately to ensure a high degree of sequence similarity This set consisted of full length sequences from different organisms,. New sequence and structure entries are assigned to existing homologous families and superfamilies based on their sequence similarity

Findings

Conclusions

Schellenberger A