Pyrimidine (PYR) binding domain of thiamine pyrophosphate (TPP)-dependent enzymes.
Thiamine pyrophosphate (TPP) family, pyrimidine (PYR) binding domain; found in many key metabolic enzymes which use TPP (also known as thiamine diphosphate) as a cofactor. TPP binds in the cleft formed by a PYR domain and a PP domain. The PYR domain, binds the aminopyrimidine ring of TPP, the PP domain binds the diphosphate residue. A polar interaction between the conserved glutamate of the PYR domain and the N1' of the TPP aminopyrimidine ring is shared by most TPP-dependent enzymes, and participates in the activation of TPP. The PYR and PP domains have a common fold, but do not share strong sequence conservation. The PP domain is not included in this group. Most TPP-dependent enzymes have the PYR and PP domains on the same subunit although these domains can be alternatively arranged in the primary structure. In the case of 2-oxoisovalerate dehydrogenase (2OXO), sulfopyruvate decarboxylase (ComDE), and the E1 component of human pyruvate dehydrogenase complex (E1- PDHc) the PYR and PP domains appear on different subunits. TPP-dependent enzymes are multisubunit proteins, the smallest catalytic unit being a dimer-of-active sites. For many of these enzymes the active sites lie between PP and PYR domains on different subunits. However, for the homodimeric enzymes 1-deoxy-D-xylulose 5-phosphate synthase (DXS) and Desulfovibrio africanus pyruvate:ferredoxin oxidoreductase (PFOR), each active site lies at the interface of the PYR and PP domains from the same subunit.
Comment:many proteins in this group are either homotetramers (dimer-of-homodimers), e.g. E. coli MenD, and L. plantarum POX, or homodimers, e.g. S. cerevisiae AHAS, D. africanus PFOR, and D. radiodurans DXS, and have two TPP-binding sites per homodimer. E1-PDHc is an alpha2beta2 dimer-of-heterodimers, having one TPP bound per heterodimer.
Comment:for some the TPP binds in a site lying between a PYR domain and a PP domain from different subunits. For others it lies between a PYR and a PP domain from the same subunit.