Dual substrate recognition of aminotransferases.
Pyridoxal 5'-phosphate-dependent aminotransferases reversibly catalyzes the transamination reaction in which the alpha-amino group of amino acid 1 is transferred to the 2-oxo acid of amino acid 2 (usually 2-oxoglutarate) to produce the 2-oxo acid of amino acid 1 and amino acid 2 (glutamate). An aminotransferase must thus be able to recognize and bind two kinds of amino acids (amino acids 1 and 2), the side chains of which are different in shape and properties, from among many other small molecules. The dual substrate recognition mechanism has been discovered based on three-dimensional structures of aromatic amino acids, histidinol phosphate, glutamine:phenylpyruvate, acetylornithine, and branched-chain amino acid aminotransferases. There are two representative strategies for dual substrate recognition. An aromatic amino acid aminotransferase prepares charged and neutral pockets for acidic and aromatic side chains, respectively, at the same place by a large-scale rearrangement of the hydrogen-bond network caused by the induced fit. In a branched-chain aminotransferase, the same hydrophobic cavity implanted with hydrophilic sites accommodates both hydrophobic and acidic side chains without side-chain rearrangements of the active-site residues, which is reminiscent of the lock and key mechanism. Dual substrate recognition in other aminotransferases is attained by combining the two representative methods.
Hirotsu
Ken
K
Graduate School of Science, Osaka City University, Osaka 558-8585, Japan. hirotsu@sci.osaka-cu.ac.jp
Goto
Masaru
M
Okamoto
Akihiro
A
Miyahara
Ikuko
I
D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007656:Ketoglutaric Acids / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D013237:Stereoisomerism; D013379:Substrate Specificity; D000637:Transaminases / Q000737:chemistry / Q000378:metabolism*; D014867:Water / Q000737:chemistry
D000596:Amino Acids; D007656:Ketoglutaric Acids; D014867:Water; D000637:Transaminases; C019798:branched-chain-amino-acid transaminase; C019729:aromatic amino acid aminotransferase