Allosteric activation and contrasting properties of L-serine dehydratase types 1 and 2.

Bacterial L-serine dehydratases differ from mammalian L- and D-serine dehydratases and bacterial D-serine dehydratases by the presence of an iron-sulfur center rather than a pyridoxyl phosphate prosthetic group. They exist in two forms, types 1 and 2, distinguished by their sequence and oligomeric configuration. Both types contain an ASB domain, and the type 1 enzymes also contain an ACT domain in a tandem arrangement with the ASB domain like that in type 1 D-3-phosphoglycerate dehydrogenases (PGDHs). This investigation reveals striking kinetic differences between L-serine dehydratases from Bacillus subtilis (bsLSD, type 1) and Legionella pneumophila (lpLSD, type 2). lpLSD is activated by monovalent cations and inhibited by monovalent anions. bsLSD is strongly activated by cations, particularly potassium, and shows a mixed response to anions. Flouride is a competitive inhibitor for lpLSD but an apparent activator for bsLSD at low concentrations and an inhibitor at high concentrations. The reaction products, pyruvate and ammonia, also act as activators but to different extents for each type. Pyruvate activation is competitive with L-serine, but activation of the enzyme is not compatible with it simply competing for binding at the active site and suggests the presence of a second, allosteric site. Because activation can be eliminated by higher levels of L-serine, it may be that this second site is actually a second serine binding site. This is consistent with type 1 PGDH in which the ASB domain functions as a second site for substrate binding and activation.

[1]  G. A. Grant,et al.  Kinetic, mutagenic, and structural homology analysis of L-serine dehydratase from Legionella pneumophila. , 2011, Archives of biochemistry and biophysics.

[2]  Elaine Newman,et al.  Deficiency in l-Serine Deaminase Interferes with One-Carbon Metabolism and Cell Wall Synthesis in Escherichia coli K-12 , 2010, Journal of bacteriology.

[3]  G. A. Grant,et al.  Role of the anion-binding site in catalysis and regulation of Mycobacterium tuberculosis D-3-phosphoglycerate dehydrogenase. , 2009, Biochemistry.

[4]  Robert G. Martin,et al.  Transcriptional activation by MarA, SoxS and Rob of two tolC promoters using one binding site: a complex promoter configuration for tolC in Escherichia coli , 2008, Molecular microbiology.

[5]  Elaine Newman,et al.  Deficiency in l‐serine deaminase results in abnormal growth and cell division of Escherichia coli K‐12 , 2008, Molecular microbiology.

[6]  G. A. Grant The ACT Domain: A Small Molecule Binding Domain and Its Role as a Common Regulatory Element* , 2006, Journal of Biological Chemistry.

[7]  D. Lawson,et al.  The iron–sulfur cluster in the l‐serine dehydratase TdcG from Escherichia coli is required for enzyme activity , 2004, FEBS letters.

[8]  Eric J. Schnitzer,et al.  Escherichia coli L-Serine Deaminase Requires a [4Fe-4S] Cluster in Catalysis* , 2004, Journal of Biological Chemistry.

[9]  A. Hofmeister,et al.  Cloning and expression of the two genes coding for L-serine dehydratase from Peptostreptococcus asaccharolyticus: relationship of the iron-sulfur protein to both L-serine dehydratases from Escherichia coli , 1997, Journal of bacteriology.

[10]  Helmut Beinert,et al.  ACONITASE AS IRON-SULFUR PROTEIN, ENZYME, AND IRON-REGULATORY PROTEIN , 1996 .

[11]  R. M. Allen,et al.  Iron−Sulfur Proteins with Nonredox Functions , 1996 .

[12]  A. Hofmeister,et al.  Iron—sulfur cluster‐containing l‐serine dehydratase from Peptostreptococcus asaccharolyticus: Correlation of the cluster type with enzymatic activity , 1994, FEBS letters.

[13]  A. Hofmeister,et al.  Bacterial L-serine dehydratases: a new family of enzymes containing iron-sulfur clusters. , 1993, Trends in biochemical sciences.

[14]  D. Linder,et al.  L-serine and L-threonine dehydratase from Clostridium propionicum. Two enzymes with different prosthetic groups. , 1993, European journal of biochemistry.

[15]  E. Newman,et al.  Sequencing and characterization of the sdaB gene from Escherichia coli K-12. , 1993, European journal of biochemistry.

[16]  W. Buckel,et al.  Purification and properties of an iron-sulfur-containing and pyridoxal-phosphate-independent L-serine dehydratase from Peptostreptococcus asaccharolyticus. , 1991, European journal of biochemistry.

[17]  E. Newman,et al.  A novel L-serine deaminase activity in Escherichia coli K-12 , 1991, Journal of bacteriology.

[18]  B. Lang,et al.  L-serine degradation in Escherichia coli K-12: cloning and sequencing of the sdaA gene , 1989, Journal of bacteriology.

[19]  C. Federiuk,et al.  Characterization of the catalytic pathway for D-serine dehydratase. Evidence for variation of the rate-determining step with substrate structure. , 1983, The Journal of biological chemistry.

[20]  C. Walsh,et al.  Letter: Stereospecific synthesis of isotopically labeled serine at carbon 3 and stereochemical analysis of D-serine dehydrase reaction. , 1976, Journal of the American Chemical Society.

[21]  R. D. Sagers,et al.  Ferrous Ion-Dependent l-Serine Dehydratase from Clostridium acidiurici , 1972, Journal of bacteriology.