期刊
FEBS JOURNAL
卷 276, 期 9, 页码 2447-2453出版社
WILEY
DOI: 10.1111/j.1742-4658.2009.06965.x
关键词
aminopyrimidine-iminopyrimidine tautomerization; carboligation; conserved glutamate; 3D structure; effective dielectric constant; glyoxylate carboligase; thiamin; thiamin diphosphate-dependent enzyme
资金
- Israel Science Foundation [716/06]
- Binational Science Foundation [2007129]
Subsequent to the demonstration in the late 1950s of the catalytic power of the C2 anion/ylid of thiamin diphosphate, further convincing evidence was provided demonstrating that the 4'-aminopyrimidine group plays a vital role in activation of this cofactor. Structural evidence from several crystal structures of thiamin diphosphate-dependent enzymes emphasized the presence of a glutamate residue in hydrogen-bonding distance from N1' as a conserved element in these enzymes. The important role of this conserved glutamate in promoting C2-H ionization and activation of thiamin diphosphate was emphasized by site-directed mutagenesis studies. This role was further elaborated by spectroscopic studies of the 4'-aminopyrimidine-iminopyrimidine tautomerization. The low polarity of the environment of the protein-bound thiazolium is an additional factor in the stabilization of the C2 anion/ylid. The recently determined crystal structure and mutagenesis studies of glyoxylate carboligase, in which the position of the conserved glutamate is occupied by valine, now show that, for the multi-step reaction catalyzed by this enzyme, the advantages of accelerating the ionization of C2-H by re-introducing a carboxylate are outweighed by the apparent overstabilization of intermediates.
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