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

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.

Systematic Analysis of Large Enzyme Families: Identification of Specificity‐ and Selectivity‐Determining Hotspots

“…[26] Currently, more than 50 000 sequences have been deposited in the ThDP-dependent Enzyme Engineering Database (www.TEED.uni-stuttgart.de), a repository of annotated sequences, structures, and multisequence alignments of ThDPdependent enzymes. [27] Although very diverse in sequence and domain organization, ThDP-dependent enzymes share two conserved protein domains, the pyrophosphate (PP) and the pyrimidine (PYR) binding domain, with the cofactor ThDP bound at their domain interface. [28] The sequences were grouped into eight superfamilies with similar domain structure, though their overall sequence similarity was low.…”

“…[28] The sequences were grouped into eight superfamilies with similar domain structure, though their overall sequence similarity was low. [27] The superfamily of ThDP-dependent decarboxylases is the most intensively studied superfamily, because of the potential of decarboxylases to catalyze the formation of mixed carboligation products from a donor substrate and an acceptor substrate with high chemo-and stereoselectivity. [29] Two members of the decarboxylase superfamily, benzoylformate decarboxylase from Pseudomonas putida (PpBFD) and benzaldehyde lyase from Pseudomonas fluorescens (PfBAL), were thoroughly characterized for carboligation of acetaldehyde and benzaldehyde, which resulted in four different a-hydroxy ketones (Scheme 2): acetoin and benzoin resulting from condensation of acetaldehyde and benzaldehyde, respectively, and the mixed carboligation products 2-hydroxypropiophenone (2-HPP, Scheme 3) from benzaldehyde as donor and acetaldehyde as acceptor, and 1-phenyl-1-hydroxypropan-2-one (phenylacetylcarbinol, PAC) from acetaldehyde as donor and benzaldehyde as acceptor.…”

A review of polioencephalomalacia in ruminants: is the development of malacic lesions associated with excess sulfur intake independent of thiamine deficiency?

“…Thiamine pyrophosphate is the metabolically active form of thiamine, being a cofactor in catalytic reaction of key enzymes: pyruvate dehydrogenase (PDH), α-ketoglutarate doi: 10.7243/2054-3425-1-1 dehydrogenase (α-KGDH) and transketolase (TK). These TPP dependent enzymes are involved in cerebral glucose and energy metabolism [81][82][83].…”

Diversität asymmetrischer Thiamin-Katalyse

“…Zum Sequenz-und Strukturvergleich von Enzymen wurde kürzlich eine Datenbank für ThDP-Proteinfamilien etabliert (www.teed.unistuttgart.de) [9].…”

“…3C) Strukturelle Anordnung der Domänen Thiamindiphosphat-abhängiger Enzyme. PP: Phosphat-Bindedomäne; PYR: Pyrimidin-Bindedomäne (entnommen aus[9] mit freundlicher Genehmigung von BMC).…”