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

Abstract

Background: 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, 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.

Description: The 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.

Conclusions: The 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.

Figure 1

Structural arrangement of protein domains of the superfamilies of the TEED. All protein families are listed with their internal superfamily ID, the superfamily name and a 2D representation of the domain arrangement.

Figure 2

Multisequence alignment of ThDP dependent proteins with annotated domains. The pyrophosphate (PP) domain is coloured in blue, the pyrimidine (PYR) domain is coloured red. Annotated PP and PYR domains are available for all protein families in the TEED. The displayed multisequence alignment is taken from the transketolase homologous protein family (TEED ID 33)