Three-dimensional structures aspartate aminotransferase

Thiosulfate cyanide sulfurtransferase symmetry in 78 TTiiouridine 234 Three-dimensional structures of aconitase 689 adenylate kinase 655 aldehyde oxido-reductase 891 D-amino acid oxidase 791 a-amylase, pancreatic 607 aspartate aminotransferase 57,135 catalytic intermediates 752 aspartate carbamyltransferase 348 aspartate chemoreceptor 562 bacteriophage P22 66 cadherin 408 calmodulin 317 carbonic acid anhydrase I 679 carboxypeptidase A 64 catalase 853 cholera toxin 333, 546 chymotrypsin 611 citrate synthase 702, 703 cutinase 134 cyclosporin 488 cytochrome c 847 cytochrome c peroxidase 849 dihydrofolate reductase 807 DNA 214, 223,228,229, 241 DNA complex... 

Aspartate aminotransferase is the prototype of a large family of PLP-dependent enzymes. Comparisons of amino acid sequences as well as several three-dimensional structures reveal that almost all transaminases having roles in amino acid biosynthesis are related to aspartate aminotransferase by divergent evolution. An examination of the aligned amino acid sequences reveals that two residues are completely conserved. These residues are the lysine residue that forms the Schiff base with the pyridoxal phosphate cofactor (lysine 258 in aspartate aminotransferase) and an arginine residue that interacts with the a-carboxylate group of the ketoacid (see Figure 23.11). 

The a subunit catalyzes the formation of indole from indole-3-glycerol phosphate, whereas each P subunit has a PLP-containing active site that catalyzes the condensation of indole and serine to form tryptophan. The overall three-dimensional structure of this enzyme is distinct from that of aspartate aminotransferase and the other PLP enzymes already discussed. Serine forms a Schiff base with this PLP, which is then dehydrated to give the Schiffbase of aminoacrylate. This reactive intermediate is attacked by indole to give tryptophan. 

Aspartate aminotransferase (AAT) is the first PLP-dependent enzyme for which the three-dimensional structure has been determined " " and is the prototype of fold-type I PLP-enzymes. Each subunit of the AAT homodimer has a large and a small domain. The coenzyme is bound to the large (N-terminal) domain and located in a pocket at the subunit interface, so that residues from each monomer contribute to the formation of both active sites. The proximal and distal carboxylate group of the dicarboxylic substrates bind to Arg386 and Arg292, respectively, the latter contributed by the opposite subunit. " Early crystallographic strucmres... 

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