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Conservation of Fold and Topology of Functional Elements in Thiamin Pyrophosphate EnzymesThiamin pyrophosphate (TPP)-dependent enzymes are a highly divergent family of proteins binding both TPP and metal ions. They perform decarboxylation-hydroxyaldehydes. Prior -ketoacids and of a common - (O=)C-C(OH)- fragment of to knowledge of three-dimensional structures of these enzmes, the GDGY25-30NN sequence was used to identify these enzymes. Subsequently, a number of structural studies on those enzymes revealed multi-subunit organization and the features of the two duplicate cofactor binding sites. Analyzing the structures of 44 structurally known enzymes, we found that the common structure of these enzymes is reduced to 180-220 amino acid long fragments of two PP and two PYR domains that form the [PP:PYR]2 binding center of two cofactor molecules. The structures of PP and PYR are arranged in a similar fold-sheet with triplets of helices on both sides.Dconsisting of a six-stranded Residues surrounding the cofactors are not strictly conserved, but they provide the same interatomic contacts required for the catalytic functions that these enzymes perform while maintaining interactive structural integrity. These structural and functional amino acids are topological counterparts located in the same positions of the conserved fold of sets of PP and PYR domains. Additional parallels include short fragments of sequences that link these amino acids to the fold and function. This report on the structural commonalities amongst TPP dependent enzymes is thought to contribute new approaches to annotation that may assist in advancing the functional proteomics of TPP dependent enzymes, and trace their complexity within evolutionary context.
Document ID
20050092342
Document Type
Preprint (Draft being sent to journal)
Authors
Dominiak, P. (NASA Marshall Space Flight Center Huntsville, AL, United States)
Ciszak, E. M. (NASA Marshall Space Flight Center Huntsville, AL, United States)
Date Acquired
August 22, 2013
Publication Date
January 1, 2005
Subject Category
Inorganic, Organic and Physical Chemistry
Distribution Limits
Public
Copyright
Work of the US Gov. Public Use Permitted.