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B6db references: 27523731

type Journal Article
authors Bezsudnova EY, Stekhanova TN, Suplatov DA, Mardanov AV
title Experimental and computational studies on the unusual substrate specificity of branched-chain amino acid aminotransferase from Thermoproteus uzoniensis
journal Arch. Biochem. Biophys.
Activity tuzn1299
Family tuzn1299
sel selected
ui 27523731
year (2016)
volume 607
pages 27-36
keywords Archaea; Branched-chain amino acid aminotransferase; Molecular modeling; Subfamily-specific positions; Substrate specificity
abstract PLP-Dependent fold-type IV branched-chain amino acid aminotransferases (BCATs) from archaea have so far been poorly characterized. A new BCAT from the hyperthermophilic archaeon Thermoproteus uzoniensis (TUZN1299) has been studied. TUZN1299 was found to be highly active toward branched-chain amino acids (BCAAs), positively charged amino acids, l-methionine, l-threonine, l-homoserine, l-glutamine, as well as toward 2-oxobutyrate and keto analogs of BCAAs, whereas l-glutamate and α-ketoglutarate were not converted in the overall reaction. According to stopped-flow experiments, the enzyme showed the highest specificity to BCAAs and their keto analogs. In order to explain the molecular mechanism of the unusual specificity of TUZN1299, bioinformatic analysis was implemented to identify the subfamily-specific positions in the aminotransferase class IV superfamily of enzymes. The role of the selected residues in binding of various ligands in the active site was further studied using molecular modeling. The results indicate that Glu188 forms a novel binding site for positively charged and polar side-chains of amino acids. Lack of accommodation for α-ketoglutarate and l-glutamate is due to the unique orientation and chemical properties of residues 102-106 in the loop forming the A-pocket. The likely functional roles of TUZN1299 in cellular metabolism - in the synthesis and degradation of BCAAs - are discussed.
last changed 2017/12/22 08:36

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