title: Substrate specificity in thiamin diphosphate-dependent decarboxylases.
abstract: Thiamin diphosphate (ThDP) is the biologically active form of vitamin B(1), and ThDP-dependent enzymes are found in all forms of life. The catalytic mechanism of this family requires the formation of a common intermediate, the 2α-carbanion-enamine, regardless of whether the enzyme is involved in C-C bond formation or breakdown, or even formation of C-N, C-O and C-S bonds. This demands that the enzymes must screen substrates prior to, and/or after, formation of the common intermediate. This review is focused on the group for which the second step is the protonation of the 2α-carbanion, i.e., the ThDP-dependent decarboxylases. Based on kinetic data, sequence/structure alignments and mutagenesis studies the factors involved in substrate specificity have been identified.
authors.affiliation: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA.
authors.forename: Forest H
authors.initials: FH
authors.lastname: Andrews
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McLeish
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D001419:Bacteria / Q000201:enzymology; D002262:Carboxy-Lyases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D006038:Glyoxylates / Q000378:metabolism; D008333:Mandelic Acids / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D019289:Pyruvic Acid / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013379:Substrate Specificity; D013835:Thiamine Pyrophosphate / Q000378:metabolism*
chemical_list: D000214:Acyl Coenzyme A; D006038:Glyoxylates; D008333:Mandelic Acids; C523110:oxalyl-coenzyme A; C012482:phenylglyoxylic acid; D019289:Pyruvic Acid; D002262:Carboxy-Lyases; D013835:Thiamine Pyrophosphate