A lysine-tyrosine pair carries out acid-base chemistry in the metal ion-dependent pyridine dinucleotide-linked beta-hydroxyacid oxidative decarboxylases.
This work reviews published structural and kinetic data on the pyridine nucleotide-linked beta-hydroxyacid oxidative decarboxylases. The family of metal ion-dependent pyridine nucleotide-linked beta-hydroxyacid oxidative decarboxylases can be divided into two structural families with the malic enzyme, which has an (S)-hydroxyacid substrate, comprising one subfamily and isocitrate dehydrogenase, isopropylmalate dehydrogenase, homoisocitrate dehydrogenase, and tartrate dehydrogenase, which have an (R)-hydroxyacid substrate, comprising the second subclass. Multiple-sequence alignment of the members of the (R)-hydroxyacid family indicates a high degree of sequence identity with most of the active site residues conserved. The three-dimensional structures of the members of the (R)-hydroxyacid family with structures available superimpose on one another, and the active site structures of the enzymes have a similar overall geometry of residues in the substrate and metal ion binding sites. In addition, a number of residues in the malic enzyme active site are also conserved, and the arrangement of these residues has a similar geometry, although the (R)-hydroxyacid and (S)-hydroxyacid family sites are geometrically mirror images of one another. The active sites of the (R)-hydroxyacid family have a higher positive charge density when compared to those of the (S)-hydroxyacid family, largely due to the number of arginine residues in the vicinity of the substrate alpha-carboxylate and one fewer carboxylate ligand to the divalent metal ion. Data available for all of the enzymes in the family have been considered, and a general mechanism that makes use of a lysine (general base)-tyrosine (general acid) pair is proposed. Differences exist in the mechanism for generating the neutral form of lysine so that it can act as a base.
Aktas
Deniz F
DF
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, 73019, USA.
Cook
Paul F
PF
D000136:Acid-Base Equilibrium; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002262:Carboxy-Lyases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D006801:Humans; D008239:Lysine / Q000737:chemistry*; D008670:Metals / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009711:Nucleotides / Q000737:chemistry*; D010084:Oxidation-Reduction; D020836:Protein Structure, Quaternary; D011725:Pyridines / Q000737:chemistry*; D016415:Sequence Alignment; D014443:Tyrosine / Q000737:chemistry*
D001426:Bacterial Proteins; D008670:Metals; D009711:Nucleotides; D011725:Pyridines; D014443:Tyrosine; D002262:Carboxy-Lyases; D008239:Lysine