DT-Web

DB00260 - Cycloserine


Identification
Name Cycloserine
Accession Number DB00260 (APRD00894, DB03123)
Type small molecule
Description Antibiotic substance produced by Streptomyces garyphalus. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 102.0919
Groups approved
Monoisotopic Weight 102.042927446
Pharmacology
Indication Used in combination with up to 5 other drugs as a treatment for Mycobacterium avium complex (MAC) and is also used to treat tuberculosis (TB).
Mechanism of action Cycloserine is an analog of the amino acid D-alanine. It interferes with an early step in bacterial cell wall synthesis in the cytoplasm by competitive inhibition of two enzymes, L-alanine racemase, which forms D-alanine from L-alanine, and D-alanylalanine synthetase, which incorporates D-alanine into the pentapeptide necessary for peptidoglycan formation and bacterial cell wall synthesis.
Absorption Rapidly and almost completely absorbed (70 to 90%) from the gastrointestinal tract following oral administration.
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Oral LD50 in mouse is 5290 mg/kg, and in rat is over 5000 mg/kg. Symptoms of a cycloserine overdose include drowsiness, confusion, headache, dizziness, irritability, numbness and tingling, difficulty speaking, paralysis, abnormal behavior, seizures, and unconsciousness.
Affected organisms
  • Enteric bacteria and other eubacteria
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


D-alanine--D-alanine ligase A
Name D-alanine--D-alanine ligase A
Gene Name ddlA
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Belanger AE, Porter JC, Hatfull GF: Genetic analysis of peptidoglycan biosynthesis in mycobacteria: characterization of a ddlA mutant of Mycobacterium smegmatis. J Bacteriol. 2000 Dec;182(23):6854-6. - Pubmed
  • Noda M, Kawahara Y, Ichikawa A, Matoba Y, Matsuo H, Lee DG, Kumagai T, Sugiyama M: Self-protection mechanism in D-cycloserine-producing Streptomyces lavendulae. Gene cloning, characterization, and kinetics of its alanine racemase and D-alanyl-D-alanine ligase, which are target enzymes of D-cycloserine. J Biol Chem. 2004 Oct 29;279(44):46143-52. Epub 2004 Aug 9. - Pubmed
  • McCoy AJ, Maurelli AT: Characterization of Chlamydia MurC-Ddl, a fusion protein exhibiting D-alanyl-D-alanine ligase activity involved in peptidoglycan synthesis and D-cycloserine sensitivity. Mol Microbiol. 2005 Jul;57(1):41-52. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.3036
Alanine racemase
Name Alanine racemase
Gene Name alr
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Feng Z, Barletta RG: Roles of Mycobacterium smegmatis D-alanine:D-alanine ligase and D-alanine racemase in the mechanisms of action of and resistance to the peptidoglycan inhibitor D-cycloserine. Antimicrob Agents Chemother. 2003 Jan;47(1):283-91. - Pubmed
  • Fenn TD, Stamper GF, Morollo AA, Ringe D: A side reaction of alanine racemase: transamination of cycloserine. Biochemistry. 2003 May 20;42(19):5775-83. - Pubmed
  • Fenn TD, Holyoak T, Stamper GF, Ringe D: Effect of a Y265F mutant on the transamination-based cycloserine inactivation of alanine racemase. Biochemistry. 2005 Apr 12;44(14):5317-27. - Pubmed
DTHybrid score 1.3035

Enzymes


Aromatic-L-amino-acid decarboxylase
Name Aromatic-L-amino-acid decarboxylase
Gene Name DDC
Actions inhibitor
References
  • DENGLER HJ, RAUCHS E, RUMMEL W: [On the inhibition of L-glutamic acid and L-DOPA decarboxylase by D-cycloserine and other isoxazolidones]. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1962;243:366-81. - Pubmed
DTHybrid score 0.8368

Transporters


Proton-coupled amino acid transporter 2
Name Proton-coupled amino acid transporter 2
Gene Name Not Available
Actions Not Available
References
  • Kennedy DJ, Gatfield KM, Winpenny JP, Ganapathy V, Thwaites DT: Substrate specificity and functional characterisation of the H+/amino acid transporter rat PAT2 (Slc36a2). Br J Pharmacol. 2005 Jan;144(1):28-41. - Pubmed
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
2453 Alanine racemase alr 1.3035
831 D(2) dopamine receptor DRD2 0.0325
6151 Monocarboxylate transporter 10 SLC16A10 0.0288
4063 Tryptophanyl-tRNA synthetase, mitochondrial WARS2 0.0238
90 Tryptophan 5-hydroxylase 2 TPH2 0.0238
23 D(1A) dopamine receptor DRD1 0.0228
694 Matrix protein 2 M 0.0226
765 Indoleamine 2,3-dioxygenase IDO1 0.0198
556 Alpha-1A adrenergic receptor ADRA1A 0.0195
252 Tryptophanyl-tRNA synthetase, cytoplasmic WARS 0.0186
1588 Multidrug resistance protein 1 ABCB1 0.0179
134 Tryptophan 5-hydroxylase 1 TPH1 0.0175
6012 Tryptophan 2,3-dioxygenase TDO2 0.0173
2452 Tryptophanyl-tRNA synthetase trpS 0.0173
199 Monocarboxylate transporter 8 SLC16A2 0.0153
866 Large neutral amino acids transporter small subunit 2 SLC7A8 0.0149
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0146
245 Large neutral amino acids transporter small subunit 1 SLC7A5 0.0136
3939 Amine oxidase [flavin-containing] B MAOB 0.0132
502 5-hydroxytryptamine 2A receptor HTR2A 0.013
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0126
6144 Solute carrier family 22 member 2 SLC22A2 0.0115
1517 Beta-3 adrenergic receptor ADRB3 0.0111
6145 Solute carrier family 22 member 1 SLC22A1 0.011
828 Phenylalanine-4-hydroxylase PAH 0.0109
3109 Phenylalanine-4-hydroxylase phhA 0.0109
163 D(1B) dopamine receptor DRD5 0.0109
432 D(4) dopamine receptor DRD4 0.0102
638 D(3) dopamine receptor DRD3 0.0099
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0086
789 Alpha-1D adrenergic receptor ADRA1D 0.0086
378 Alpha-2C adrenergic receptor ADRA2C 0.0083
629 Alpha-2B adrenergic receptor ADRA2B 0.0082
193 Beta-1 adrenergic receptor ADRB1 0.0079
766 Beta-2 adrenergic receptor ADRB2 0.0077
632 Alpha-1B adrenergic receptor ADRA1B 0.0077
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0076
318 Alpha-2A adrenergic receptor ADRA2A 0.0073
4119 Cytochrome P450 2D6 CYP2D6 0.0061
3893 DDC protein DDC 0.0038
3891 Putative L-Dopa decarboxylase DDC 0.0037
3908 P-selectin cytoplasmic tail-associated protein pcap 0.0031
3896 CDNA FLJ46802 fis, clone TRACH3032150, moderately similar to Cysteine sulfinic acid decarboxylase GADL1 0.0031
3911 Uncharacterized protein C20orf38 SPTLC3 0.0031
3906 Serine dehydratase-like SDSL 0.0031
3881 Selenocysteine lyase variant Not Available 0.0031
3887 Phosphorylase PYGB 0.0031
3915 Cysteine sulfinic acid decarboxylase-related protein 1 CSAD 0.0031
3914 Alanine-glyoxylate aminotransferase homolog TLH6 0.0031
3878 GAD1 protein GAD1 0.0031
3883 Ornithine aminotransferase variant Not Available 0.0031
306 Pyridoxal phosphate phosphatase PDXP 0.0031
664 Glutamate decarboxylase 2 GAD2 0.0031
3890 Glutamate decarboxylase 2 GAD2 0.0031
3909 Hepatic peroxysomal alanine:glyoxylate aminotransferase Not Available 0.0031
855 Sphingosine-1-phosphate lyase 1 SGPL1 0.0031
3880 Serine hydroxymethyltransferase 1 Not Available 0.0031
3910 O-phosphoseryl-tRNA(Sec) selenium transferase SEPSECS 0.0031
3894 KIAA0251 protein PDXDC1 0.0031
3875 Glycogen phosphorylase, brain form PYGB 0.0031
3882 Brain glycogen phosphorylase variant Not Available 0.0031
3903 Aminolevulinate, delta-, synthase 2 ALAS2 0.0031
3886 Migration-inducing protein 4 ALAS1 0.0031
3905 Molybdenum cofactor sulfurase MOCOS 0.0031
3913 Glutamic acid decarboxylase GAD65 0.0027
3 Histidine decarboxylase HDC 0.0027
727 Serine palmitoyltransferase 2 SPTLC2 0.0026
491 Serine palmitoyltransferase 1 SPTLC1 0.0026
184 L-serine dehydratase SDS 0.0026
431 Serine racemase SRR 0.0026
3874 Proline synthetase co-transcribed bacterial homolog protein PROSC 0.0026
89 Cysteine sulfinic acid decarboxylase CSAD 0.0026
3899 Alanine--glyoxylate aminotransferase 2-like 2 AGXT2L2 0.0026
534 Threonine synthase-like 1 THNSL1 0.0026
420 Glutamate decarboxylase 1 GAD1 0.0026
3900 Glutamate decarboxylase 1 GAD1 0.0026
665 Phosphoserine aminotransferase PSAT1 0.0026
4652 Phosphoserine aminotransferase serC 0.0026
3895 Kynurenine--oxoglutarate transaminase 3 CCBL2 0.0026
801 Kynurenine/alpha-aminoadipate aminotransferase mitochondrial AADAT 0.0026
575 2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial GCAT 0.0026
455 5-aminolevulinate synthase, nonspecific, mitochondrial ALAS1 0.0026
681 Glycine dehydrogenase [decarboxylating], mitochondrial GLDC 0.0026
499 Arginine decarboxylase ADC 0.0026
435 Kynureninase KYNU 0.0024
4654 Kynureninase kynU 0.0024
763 Tyrosine aminotransferase TAT 0.0024
5493 Tyrosine aminotransferase Not Available 0.0024
169 Cysteine desulfurase, mitochondrial NFS1 0.0024
3877 Growth-inhibiting protein 18 GIG18 0.0024
358 Cystathionine beta-synthase CBS 0.0023
3884 SHMT2 protein SHMT2 0.0023
3901 SHMT2 protein SHMT2 0.0023
3885 Hypothetical protein DKFZp686P09201 DKFZp686P09201 0.0023
3879 Serine hydroxymethyltransferase 2 Not Available 0.0023
321 Serine hydroxymethyltransferase, mitochondrial SHMT2 0.0023
203 Pyridoxine-5'-phosphate oxidase PNPO 0.0023
472 Ornithine aminotransferase, mitochondrial OAT 0.0023
735 Alanine aminotransferase 1 GPT 0.0023
3904 Alanine aminotransferase 2 GPT2 0.0023
426 Aspartate aminotransferase, mitochondrial GOT2 0.0023
914 Formimidoyltransferase-cyclodeaminase FTCD 0.0022
301 Kynurenine--oxoglutarate transaminase 1 CCBL1 0.0022
114 Alanine--glyoxylate aminotransferase 2, mitochondrial AGXT2 0.0022
868 Cystathionine gamma-lyase CTH 0.0022
586 Aspartate aminotransferase, cytoplasmic GOT1 0.0021
349 Serine--pyruvate aminotransferase AGXT 0.002
795 Branched-chain-amino-acid aminotransferase, mitochondrial BCAT2 0.002
367 Serine hydroxymethyltransferase, cytosolic SHMT1 0.002
574 Branched-chain-amino-acid aminotransferase, cytosolic BCAT1 0.002
449 Ornithine decarboxylase ODC1 0.002
280 4-aminobutyrate aminotransferase, mitochondrial ABAT 0.0019
10 Glycogen phosphorylase, liver form PYGL 0.0018
1152 Glycogen phosphorylase, muscle form PYGM 0.0014
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