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Structural basis for chiral substrate recognition by two 2,3‐butanediol dehydrogenases
Author(s) -
Otagiri Masato,
Ui Sadaharu,
Takusagawa Yuhsuke,
Ohtsuki Takashi,
Kurisu Genji,
Kusunoki Masami
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.11.068
Subject(s) - stereospecificity , stereochemistry , chemistry , biochemistry , dehydrogenase , enzyme , residue (chemistry) , substrate (aquarium) , nad+ kinase , biology , catalysis , ecology
2,3‐Butanediol dehydrogenase (BDH) catalyzes the NAD‐dependent redox reaction between acetoin and 2,3‐butanediol. There are three types of homologous BDH, each stereospecific for both substrate and product. To establish how these homologous enzymes possess differential stereospecificities, we determined the crystal structure of l ‐BDH with a bound inhibitor at 2.0 Å. Comparison with the inhibitor binding mode of meso ‐BDH highlights the role of a hydrogen‐bond from a conserved Trp residue 192 . Site‐directed mutagenesis of three active site residues of meso ‐BDH, including Trp 190 , which corresponds to Trp 192 of l ‐BDH, converted its stereospecificity to that of l ‐BDH. This result confirms the importance of conserved residues in modifying the stereospecificity of homologous enzymes.