MF7000061 YdcE 1gyj X-ray 2.10 Homodimer Escherichia coli 12356301 Almrud JJ, Kern AD, Wang SC, Czerwinski RM, Johnson WH, Murzin AG, Hackert ML, Whitman CP Biochemistry 2002 40 41 12010-24 The tautomerase superfamily consists of three major families represented by 4-oxalocrotonate tautomerase (4-OT), 5-(carboxymethyl)-2-hydroxymuconate isomerase (CHMI), and macrophage migration inhibitory factor (MIF). The members of this superfamily are structurally homologous proteins constructed from a simple beta-alpha-beta fold that share a key mechanistic feature; they use an amino-terminal proline, which has an unusually low pK(a), as the general base in a keto-enol tautomerization. Several new members of the 4-OT family have now been identified using PSI-BLAST and categorized into five subfamilies on the basis of multiple-sequence alignments and the conservation of key catalytic and structural residues. The members of subfamily 5, which includes a hypothetical protein designated YdcE from Escherichia coli, are predicted not to form hexamers. The crystal structure of YdcE has been determined to 1.35 A resolution and confirms that it is a dimer. In addition, YdcE complexed with (E)-2-fluoro-p-hydroxycinnamate, identified as a potent competitive inhibitor of this enzyme, as well as N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid (HEPES) and benzoate are also presented. These latter crystal structures reveal the location of the active site and suggest a mechanism for the observed YdcE-catalyzed tautomerization reaction. The dimeric arrangement of YdcE represents a new structure in the 4-OT family and demonstrates structural diversity within the 4-OT family not previously reported. GO:0016862 intramolecular oxidoreductase activity, interconverting keto- and enol-groups GO:0042803 protein homodimerization activity GO:0005737 cytoplasm GO:0006725 cellular aromatic compound metabolic process 2 1 Homooligomeric enzymes Homodimeric enzymes All chains according to the most probable oligomerization state stored in PDBe were considered. A Tautomerase PptA Escherichia coli P31992 2 77 98% MPHIDIKCFPRELDEQQKAALAADITDVIIRHLNSKDSSISIALQQIQPESWQAIWDAEIAPQMEALIKKPGYSMNA 77 secondary structure helix 13 33 secondary structure helix 35 39 secondary structure helix 50 58 secondary structure helix 59 63 secondary structure strand 2 7 secondary structure strand 40 45 pfam PF01361 Tautomerase enzyme 2 54 B Tautomerase PptA Escherichia coli P31992 2 77 98% MPHIDIKCFPRELDEQQKAALAADITDVIIRHLNSKDSSISIALQQIQPESWQAIWDAEIAPQMEALIKKPGYSMNA 77 secondary structure helix 13 33 secondary structure helix 47 58 secondary structure helix 59 66 secondary structure strand 2 7 secondary structure strand 40 45 pfam PF01361 Tautomerase enzyme 2 54 Direct evidence The full structure participates in mutual synergistic folding. Tautomerase enzyme Two-state unfolding from dimers to unfolded monomers proved experimentally (PMID:11914096). A N/A B N/A MF7000061 MF7000062 MF7000063