Structural highlights
Function
TDCB_SALTY Catalyzes the anaerobic formation of alpha-ketobutyrate and ammonia from threonine in a two-step reaction. The first step involved a dehydration of threonine and a production of enamine intermediates (aminocrotonate), which tautomerizes to its imine form (iminobutyrate). Both intermediates are unstable and short-lived. The second step is the nonenzymatic hydrolysis of the enamine/imine intermediates to form 2-ketobutyrate and free ammonia. In the low water environment of the cell, the second step is accelerated by RidA. TdcB also dehydrates serine to yield pyruvate via analogous enamine/imine intermediates.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Two different pyridoxal 5'-phosphate-containing l-threonine deaminases (EC 4.3.1.19), biosynthetic and biodegradative, which catalyze the deamination of l-threonine to alpha-ketobutyrate, are present in Escherichia coli and Salmonella typhimurium. Biodegradative threonine deaminase (TdcB) catalyzes the first reaction in the anaerobic breakdown of l-threonine to propionate. TdcB, unlike the biosynthetic threonine deaminase, is insensitive to l-isoleucine and is activated by AMP. In the present study, TdcB from S. typhimurium was cloned and overexpressed in E. coli. In the presence of AMP or CMP, the recombinant enzyme was converted to the tetrameric form accompanied by significant enzyme activation. To provide insights into ligand-mediated oligomerization and enzyme activation, crystal structures of S. typhimurium TdcB and its complex with CMP were determined. In the native structure, TdcB is in a dimeric form, whereas in the TdcB.CMP complex, it exists in a tetrameric form with 222 symmetry and appears as a dimer of dimers. Tetrameric TdcB binds to four molecules of CMP, two at each of the dimer interfaces. Comparison of the dimer structure in the ligand (CMP)-free and -bound forms suggests that the changes induced by ligand binding at the dimer interface are essential for tetramerization. The differences observed in the tertiary and quaternary structures of TdcB in the absence and presence of CMP appear to account for enzyme activation and increased binding affinity for l-threonine. Comparison of TdcB with related pyridoxal 5'-phosphate-dependent enzymes points to structural and mechanistic similarities.
Crystal structures of Salmonella typhimurium biodegradative threonine deaminase and its complex with CMP provide structural insights into ligand-induced oligomerization and enzyme activation.,Simanshu DK, Savithri HS, Murthy MR J Biol Chem. 2006 Dec 22;281(51):39630-41. Epub 2006 Oct 17. PMID:17046821[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Simanshu DK, Savithri HS, Murthy MR. Crystal structures of Salmonella typhimurium biodegradative threonine deaminase and its complex with CMP provide structural insights into ligand-induced oligomerization and enzyme activation. J Biol Chem. 2006 Dec 22;281(51):39630-41. Epub 2006 Oct 17. PMID:17046821 doi:http://dx.doi.org/10.1074/jbc.M605721200
- ↑ Simanshu DK, Savithri HS, Murthy MR. Crystal structures of Salmonella typhimurium biodegradative threonine deaminase and its complex with CMP provide structural insights into ligand-induced oligomerization and enzyme activation. J Biol Chem. 2006 Dec 22;281(51):39630-41. Epub 2006 Oct 17. PMID:17046821 doi:http://dx.doi.org/10.1074/jbc.M605721200
