Escherichia coli K-12 substr. MG1655 Enzyme: D-serine ammonia-lyase

Gene: dsdA Accession Numbers: EG10249 (EcoCyc), b2366, ECK2362

Regulation Summary Diagram: ?

Regulation summary diagram for dsdA

It was established long ago that E. coli is able to deaminate serine [Gale38] and that the activity is inducible by D-serine [Pardee55, McFall64, McFall64a]. D-serine ammonia-lyase (DsdA) catalyzes the deamination of D-serine to form pyruvate and ammonia. D-serine has a bacteriostatic effect on E. coli; thus, when D-serine is present, detoxification is necessary for cell growth [McFall64]. Once the cell expresses DsdA, D-serine can be utilized as the sole source of carbon and nitrogen [Bloom75]. Toxicity of D-serine in minimal medium appears to be due to an effect on biosynthesis of L-serine and pantothenate [Cosloy73].

The cofactor requirements and reaction mechanism of the enzyme have been investigated. Binding of the pyridoxal phosphate (PLP) cofactor has been studied in detail [Reed79, Schnackerz79, Kojiro89, Marceau89, Schnackerz99]. The reaction involves a transient Schiff base intermediate of α-aminoacrylate and PLP [Schnackerz79a]. The G279D and G281D mutations eliminate enzyme activity [Marceau88] due to altered interactions with PLP [Marceau88a]. More conservative substitutions at G278, G279, and G281 result in reduced or altered enzymatic activity [Marceau90].

Crystal structures of the enzyme have been solved, confirming results from the analysis of mutant enzymes, and leading to the proposal of a catalytic mechanism [Urusova11].

Regulation of DsdA expression has been extensively investigated and was shown to involve positive regulation by DsdC and cAMP-CRP [McFall71, McFall73, Bloom75a, Bloom75, Bloom75b, Heincz78, Heincz78a, Heincz78b, NorregaardMadse95].

DsdA: "D-serine deaminase" [McFall64]

Citations: [McFall67, McFall70, McFall75, Schonbeck75, Heincz75, Heincz76, Carothers80, Schnackerz80, Federiuk81, Schiltz81, McFall83, Metzler91]

Gene Citations: [BornsteinForst87]

Locations: cytosol

Map Position: [2,477,224 -> 2,478,552] (53.39 centisomes, 192°)
Length: 1329 bp / 442 aa

Molecular Weight of Polypeptide: 47.901 kD (from nucleotide sequence), 45.5 kD (experimental) [Dowhan70 ]

pI: 5.9

Unification Links: ASAP:ABE-0007804 , CGSC:834 , EchoBASE:EB0245 , EcoGene:EG10249 , EcoliWiki:b2366 , ModBase:P00926 , OU-Microarray:b2366 , PortEco:dsdA , PR:PRO_000022485 , Pride:P00926 , Protein Model Portal:P00926 , RefSeq:NP_416867 , RegulonDB:EG10249 , SMR:P00926 , String:511145.b2366 , UniProt:P00926

Relationship Links: InterPro:IN-FAMILY:IPR000634 , InterPro:IN-FAMILY:IPR001926 , InterPro:IN-FAMILY:IPR011780 , Panther:IN-FAMILY:PTHR10314:SF9 , PDB:Structure:3SS7 , PDB:Structure:3SS9 , Pfam:IN-FAMILY:PF00291 , Prosite:IN-FAMILY:PS00165

In Paralogous Gene Group: 362 (8 members)

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for dsdA

GO Terms:

Biological Process: GO:0006974 - cellular response to DNA damage stimulus Inferred from experiment [Khil02]
GO:0036088 - D-serine catabolic process Inferred from experiment [McFall64, Dupourque66]
GO:0051410 - detoxification of nitrogen compound Inferred from experiment [McFall64]
GO:0070178 - D-serine metabolic process Inferred from experiment [Dupourque66]
GO:0006520 - cellular amino acid metabolic process Inferred by computational analysis [GOA01a]
GO:0046416 - D-amino acid metabolic process Inferred by computational analysis [GOA06, GOA01a]
Molecular Function: GO:0008721 - D-serine ammonia-lyase activity Inferred from experiment Inferred by computational analysis [GOA01, GOA01a, Labow66, Dupourque66]
GO:0016836 - hydro-lyase activity Inferred from experiment Inferred by computational analysis [GOA06, Dowhan70]
GO:0030170 - pyridoxal phosphate binding Inferred from experiment Inferred by computational analysis [GOA01a, Dupourque66, Labow66, Kazarinoff76]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005737 - cytoplasm Inferred from experiment [Dowhan70]
GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08]

MultiFun Terms: metabolism carbon utilization amino acids

Essentiality data for dsdA knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 1]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 2]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 1]
Yes [Feist07, Comment 3]

Last-Curated ? 05-Jan-2012 by Keseler I , SRI International

Enzymatic reaction of: D-serine ammonia-lyase

Synonyms: D-serine dehydratase, D-serine dehydrase, D-hydroxyaminoacid dehydratase, D-serine hydro-lyase (deaminating), D-serine deaminase

D-serine <=> 2-aminoprop-2-enoate + H2O + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.

Alternative Substrates for D-serine: D-threonine [Labow66 , Dupourque66 ]

In Pathways: D-serine degradation

The enzyme was initially characterized in E. coli Crookes strain [Metzler52] and E. coli B [Pardee55].

Cofactors or Prosthetic Groups: pyridoxal 5'-phosphate [Comment 4, Labow66, Dupourque66]

Inhibitors (Competitive): L-serine (Kic = 3000µM) [Labow66, Schnackerz99] , 2,3-diaminopropanoate (Kic = 35µM) [Schnackerz99] , O-methylserine (Kic = 1300µM) [Dupourque66, Labow66] , D-threonine (Kic = 3400µM) [Dupourque66, Comment 5]

Inhibitors (Unknown Mechanism): DL-allothreonine [Labow66]

Kinetic Parameters:

Km (μM)
kcat (sec-1)
kcat/Km (sec-1 μM-1)
[Schnackerz99, BRENDA14]
[Shleper05, BRENDA14]

T(opt): 37 °C [BRENDA14, Anfora07]

pH(opt): 7.8 [BRENDA14, Dupourque66], 7.8-8 [Dupourque66]

Sequence Features

Protein sequence of D-serine ammonia-lyase with features indicated

Feature Class Location Citations Comment
Sequence-Conflict 34
[Schiltz81, UniProt10]
UniProt: (in Ref. 5; AA sequence);
N6-pyridoxal-phosphate-Lys-Modification 118
UniProt: N6-(pyridoxal phosphate)lysine.
Modified-Residue 118
[UniProt10, Schiltz76, Marceau89]
UniProt: N6-(pyridoxal phosphate)lysine;
Sequence-Conflict 204
[Marceau88, UniProt10]
UniProt: (in Ref. 1; AAA87975);

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b2366 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10249; confirmed by SwissProt match.


Anfora07: Anfora AT, Haugen BJ, Roesch P, Redford P, Welch RA (2007). "Roles of serine accumulation and catabolism in the colonization of the murine urinary tract by Escherichia coli CFT073." Infect Immun 75(11);5298-304. PMID: 17785472

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Bloom75: Bloom FR, McFall E (1975). "Isolation and characterization of D-serine deaminase constitutive mutants by utilization of D-serine as sole carbon or nitrogen source." J Bacteriol 121(3);1078-84. PMID: 1090588

Bloom75a: Bloom FR (1975). "Isolation and characterization of catabolite-resistant mutants in the D-serine deaminase system of Escherichia coli K-12." J Bacteriol 121(3);1085-91. PMID: 163811

Bloom75b: Bloom FR, McFall E, Young MC, Carothers AM (1975). "Positive control in the D-serine deaminase system of Escherichia coli K-12." J Bacteriol 121(3);1092-101. PMID: 1090589

BornsteinForst87: Bornstein-Forst SM, McFall E, Palchaudhuri S (1987). "In vivo D-serine deaminase transcription start sites in wild-type Escherichia coli and in dsdA promoter mutants." J Bacteriol 1987;169(3);1056-60. PMID: 3029015

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014."

Carothers80: Carothers AM, McFall E, Palchaudhuri S (1980). "Physical mapping of the Escherichia coli D-serine deaminase region: contiguity of the dsd structural and regulatory genes." J Bacteriol 1980;142(1);174-84. PMID: 6246062

Cosloy73: Cosloy SD, McFall E (1973). "Metabolism of D-serine in Escherichia coli K-12: mechanism of growth inhibition." J Bacteriol 114(2);685-94. PMID: 4574697

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Dowhan70: Dowhan W, Snell EE (1970). "D-serine dehydratase from Escherichia coli. II. Analytical studies and subunit structure." J Biol Chem 245(18);4618-28. PMID: 4917239

Dowhan70a: Dowhan W, Snell EE (1970). "D-serine dehydratase from Escherichia coli. 3. Resolution of pyridoxal 5'-phosphate and coenzyme specificity." J Biol Chem 245(18);4629-35. PMID: 4917240

Dupourque66: Dupourque D, Newton WA, Snell EE (1966). "Purification and properties of D-serine dehydrase from Escherichia coli." J Biol Chem 1966;241(5);1233-8. PMID: 5327100

Federiuk81: Federiuk CS, Shafer JA (1981). "Inactivation of D-serine dehydratase by alkylamines via a transimination of enzyme-linked cofactor." J Biol Chem 256(14);7416-23. PMID: 7019208

Federiuk83: Federiuk CS, Bayer R, Shafer JA (1983). "Characterization of the catalytic pathway for D-serine dehydratase. Evidence for variation of the rate-determining step with substrate structure." J Biol Chem 258(9);5379-85. PMID: 6406501

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Gale38: Gale EF, Stephenson M (1938). "Factors influencing bacterial deamination: Factors influencing the activity of dl-serine deaminase in Bacterium coli." Biochem J 32(2);392-404. PMID: 16746632

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Heincz75: Heincz MC, McFall E (1975). "N-terminal amino acid sequences of D-serine deaminases of wild-type and operator-constitutive strains of Escherichia coli K-12." J Bacteriol 123(3);1163-8. PMID: 1099073

Heincz76: Heincz MC, McFall E (1976). "Specific in vivo cleavage of D-serine deaminase and properties of tetrameric polypeptide aggregates of the fragments." J Bacteriol 126(1);132-9. PMID: 770418

Heincz78: Heincz MC, Kelker NE, McFall E (1978). "Positive control of D-serine deaminase synthesis in vitro." Proc Natl Acad Sci U S A 75(4);1695-9. PMID: 347444

Heincz78a: Heincz MC, McFall E (1978). "Role of small molecules in regulation of D-serine deaminase synthesis." J Bacteriol 136(1);104-10. PMID: 213417

Heincz78b: Heincz MC, McFall E (1978). "Role of the dsdC activator in regulation of D-serine deaminase synthesis." J Bacteriol 136(1);96-103. PMID: 213419

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kazarinoff76: Kazarinoff MN, Snell EE (1976). "D-Serine dehydratase from Escherichia coli. Essential arginine residue at the pyridoxal 5'-phosphate binding site." J Biol Chem 251(20);6179-82. PMID: 789365

Khil02: Khil PP, Camerini-Otero RD (2002). "Over 1000 genes are involved in the DNA damage response of Escherichia coli." Mol Microbiol 44(1);89-105. PMID: 11967071

Kojiro89: Kojiro CL, Marceau M, Shafer JA (1989). "Effect of potassium ion on the phosphorus-31 nuclear magnetic resonance spectrum of the pyridoxal 5'-phosphate cofactor of Escherichia coli D-serine dehydratase." Arch Biochem Biophys 1989;268(1);67-73. PMID: 2643389

Labow66: Labow R, Robinson WG (1966). "Crystalline D-serine dehydrase." J Biol Chem 1966;241(5);1239-43. PMID: 5327101

Marceau88: Marceau M, McFall E, Lewis SD, Shafer JA (1988). "D-serine dehydratase from Escherichia coli. DNA sequence and identification of catalytically inactive glycine to aspartic acid variants." J Biol Chem 1988;263(32);16926-33. PMID: 3053699

Marceau88a: Marceau M, Lewis SD, Shafer JA (1988). "The glycine-rich region of Escherichia coli D-serine dehydratase. Altered interactions with pyridoxal 5'-phosphate produced by substitution of aspartic acid for glycine." J Biol Chem 263(32);16934-41. PMID: 3053700

Marceau89: Marceau M, Lewis SD, Kojiro CL, Shafer JA (1989). "Contribution of a conserved arginine near the active site of Escherichia coli D-serine dehydratase to cofactor affinity and catalytic activity." J Biol Chem 264(5);2753-7. PMID: 2644271

Marceau90: Marceau M, Lewis SD, Kojiro CL, Mountjoy K, Shafer JA (1990). "Disruption of active site interactions with pyridoxal 5'-phosphate and substrates by conservative replacements in the glycine-rich loop of Escherichia coli D-serine dehydratase." J Biol Chem 265(33);20421-9. PMID: 2243098

McFall64: McFall E (1964). "Genetic structure of the D-serine deaminase system of Escherichia coli." J Mol Biol 9;746-53. PMID: 14216615

McFall64a: McFall E (1964). "Pleiotropic mutations in the D-serine deaminase system of Escherichia coli." J Mol Biol 9;754-62. PMID: 14216616

McFall67: McFall E (1967). "Mapping of the d-serine deaminase region in Escherichia coli K-12." Genetics 55(1);91-9. PMID: 5340178

McFall70: McFall E, Heincz MC (1970). "Thermosensitive regulation of D-serine deaminase synthesis in a mutant of Escherichia coli K 12." Mol Gen Genet 106(4);371-7. PMID: 4921210

McFall71: McFall E, Bloom FR (1971). "Catabolite repression in the D-serine deaminase system of Escherichia coli K-12." J Bacteriol 105(1);241-8. PMID: 4322347

McFall73: McFall E (1973). "Role of adenosine 3',5'-cyclic monophosphate and its specific binding protein in the regulation of D-serine deaminase synthesis." J Bacteriol 113(2);781-5. PMID: 4347927

McFall75: McFall E (1975). "Escherichia coli K-12 mutant forming a temperature-sensitive D-serine deaminase." J Bacteriol 121(3);1074-7. PMID: 1090587

McFall83: McFall E, Runkel L (1983). "DNA sequences of the D-serine deaminase control region and N-terminal portion of the structural gene." J Bacteriol 154(3);1508-12. PMID: 6343359

Metzler52: Metzler DE, Snell EE (1952). "Deamination of serine. II. D-Serine dehydrase, a vitamin B6 enzyme from Escherichia coli." J Biol Chem 198(1);363-73. PMID: 12999751

Metzler91: Metzler CM, Metzler DE, Kintanar A, Scott RD, Marceau M (1991). "NMR spectra of exchangeable protons of pyridoxal phosphate-dependent enzymes." Biochem Biophys Res Commun 178(1);385-92. PMID: 2069576

NorregaardMadse95: Norregaard-Madsen M, McFall E, Valentin-Hansen P (1995). "Organization and transcriptional regulation of the Escherichia coli K-12 D-serine tolerance locus." J Bacteriol 1995;177(22);6456-61. PMID: 7592420

Pardee55: Pardee AB, Prestidge LS (1955). "Induced formation of serine and threonine deaminases by Escherichia coli." J Bacteriol 70(6);667-74. PMID: 13271312

Reed79: Reed TA, Schnackerz KD (1979). "The kinetics of Schiff-base formation during reconstitution of D-serine apodehydratase from Escherichia coli with pyridoxal 5'-phosphate." Eur J Biochem 94(1);207-14. PMID: 374078

Schiltz76: Schiltz E, Schnackerz KD (1976). "Sequence studies on D-serine dehydratase of Escherichia coli. Primary structure of the tryptic phosphopyridoxyl peptide and of the N-terminus." Eur J Biochem 71(1);109-16. PMID: 795658

Schiltz81: Schiltz E, Schmitt W (1981). "Sequence of Escherichia coli D-serine dehydratase. Location of the pyridoxal-phosphate binding site." FEBS Lett 134(1);57-62. PMID: 9222324

Schnackerz79: Schnackerz KD, Feldmann K, Hull WE (1979). "Phosphorus-31 nuclear magnetic resonance study of D-serine dehydratase: pryridoxal phosphate binding site." Biochemistry 18(8);1536-9. PMID: 34429

Schnackerz79a: Schnackerz KD, Ehrlich JH, Giesemann W, Reed TA (1979). "Mechanism of action of D-serine dehydratase. Identification of a transient intermediate." Biochemistry 18(16);3557-63. PMID: 383145

Schnackerz80: Schnackerz KD, Feldmann K (1980). "Pyridoxal-5'-deoxymethylenephosphonate reconstituted D-serine dehydratase: a phosphorus-31 nuclear magnetic resonance study." Biochem Biophys Res Commun 95(4);1832-8. PMID: 6998484

Schnackerz99: Schnackerz KD, Tai CH, Potsch RK, Cook PF (1999). "Substitution of pyridoxal 5'-phosphate in D-serine dehydratase from Escherichia coli by cofactor analogues provides information on cofactor binding and catalysis." J Biol Chem 274(52);36935-43. PMID: 10601247

Schonbeck75: Schonbeck ND, Skalski M, Shafer JA (1975). "Resolution of D-serine dehydratase by cysteine. An analytical treatment." J Biol Chem 250(14);5352-8. PMID: 1095577

Shleper05: Shleper M, Kartvelishvily E, Wolosker H (2005). "D-serine is the dominant endogenous coagonist for NMDA receptor neurotoxicity in organotypic hippocampal slices." J Neurosci 25(41);9413-7. PMID: 16221850

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 00:00:00." Database.

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Urusova11: Urusova DV, Isupov MN, Antonyuk S, Kachalova GS, Oblomova G, Vagin AA, Lebedev AA, Bourenko GP, Dauter Z, Bartunik HD, Lamzin VS, Melik-Adamyan WR, Mueller TD, Schnackerz KD (2011). "Crystal structure of D-serine dehydratase from Escherichia coli." Biochim Biophys Acta. PMID: 22197591

Other References Related to Gene Regulation

McFall86: McFall E (1986). "cis-acting proteins." J Bacteriol 1986;167(2);429-32. PMID: 3015868

McFall91: McFall E, Nikam SS, Palchaudhuri S (1991). "Effects of structural changes in the dsdA-dsdC intergenic region on D-serine deaminase synthesis." J Bacteriol 173(3);1161-7. PMID: 1899415

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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