Phosphopantothenate—cysteine ligase

phosphopantothenate-cysteine ligase
Identifiers
EC number 6.3.2.5
CAS number 9023-50-1
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO

In enzymology, a phosphopantothenate-cysteine ligase also known as phosphopantothenoylcysteine synthetase (PPCS) is an enzyme that catalyzes the chemical reaction which constitutes the second of five steps involved in the conversion of pantothenate to Coenzyme A. The reaction is:

NTP + (R)-4'-phosphopantothenate + L-cysteine NMP + diphosphate + N-[(R)-4'-phosphopantothenoyl]-L-cysteine

The nucleoside triphosphate (NTP) involved in the reaction varies from species to species. Phosphopantothenate—cysteine ligase from the bacterium Escherichia coli uses cytidine triphosphate (CTP) as an energy donor, whilst the human isoform uses adenosine triphosphate (ATP).[1]

Nomenclature

This enzyme belongs to the family of ligases, specifically those forming carbon-nitrogen bonds as acid-D-amino-acid ligases (peptide synthases). The systematic name of this enzyme class is (R)-4'-phosphopantothenate:L-cysteine ligase. This enzyme is also called phosphopantothenoylcysteine synthetase.

Gene

PPCS
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPPCS, Phosphopantothenate—cysteine ligase, phosphopantothenoylcysteine synthetase
External IDsMGI: 1915237 HomoloGene: 6173 GeneCards: PPCS
Gene location (Human)
Chr.Chromosome 1 (human)[2]
Band1p34.2Start42,456,117 bp[2]
End42,473,385 bp[2]
Orthologs
SpeciesHumanMouse
Entrez

79717

106564

Ensembl

ENSG00000127125

ENSMUSG00000028636

UniProt

Q9HAB8

Q8VDG5

RefSeq (mRNA)

NM_026494
NM_001355214

RefSeq (protein)

NP_080770
NP_001342143

Location (UCSC)Chr 1: 42.46 – 42.47 MbChr 4: 119.42 – 119.42 Mb
PubMed search[4][5]
Wikidata
View/Edit HumanView/Edit Mouse

Phosphopantothenoylcysteine synthetase in humans is encoded by the PPCS gene.[6]

Protein structure

As of late 2007, 5 structures have been solved for this class of enzymes, with PDB accession codes 1P9O, 1U7U, 1U7W, 1U7Z, and 1U80.

References

  1. ↑ Manoj N, Strauss E, Begley TP, Ealick SE (Aug 2003). "Structure of human phosphopantothenoylcysteine synthetase at 2.3 A resolution". Structure. 11 (8): 927–936. doi:10.1016/S0969-2126(03)00146-1. PMID 12906824.
  2. 1 2 3 GRCh38: Ensembl release 89: ENSG00000127125 - Ensembl, May 2017
  3. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028636 - Ensembl, May 2017
  4. ↑ "Human PubMed Reference:".
  5. ↑ "Mouse PubMed Reference:".
  6. ↑ "Entrez Gene: Phosphopantothenoylcysteine synthetase".

Further reading

  • Brown GM (1959). "The metabolism of pantothenic acid". J. Biol. Chem. 234 (2): 370&ndash, 8. PMID 13630913.
  • Strauss E, Kinsland C, Ge Y, McLafferty FW, Begley TP (2001). "Phosphopantothenoylcysteine synthetase from Escherichia coli Identification and characterization of the last unidentified coenzyme A biosynthetic enzyme in bacteria". J. Biol. Chem. 276 (17): 13513&ndash, 6. doi:10.1074/jbc.C100033200. PMID 11278255.
  • Kupke T (2002). "Molecular characterization of the 4'-phosphopantothenoylcysteine synthetase domain of bacterial dfp flavoproteins". J. Biol. Chem. 277 (39): 36137&ndash, 45. doi:10.1074/jbc.M206188200. PMID 12140293.
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