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 / EGO
Search PMC articles PubMed articles NCBI proteins

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 $\rightleftharpoons$ 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

Phosphopantothenoylcysteine synthetase
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1P9O​
Identifiers
Symbol	PPCS
External IDs	OMIM: 609853 HomoloGene: 6173 GeneCards: PPCS Gene
EC number	6.3.2.5
Gene ontology Molecular function • phosphopantothenate--cysteine ligase activity Cellular component • cytosol • extracellular exosome Biological process • vitamin metabolic process • water-soluble vitamin metabolic process • coenzyme biosynthetic process • coenzyme A biosynthetic process • pantothenate metabolic process • small molecule metabolic process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	79717	106564
Ensembl	ENSG00000127125	ENSMUSG00000028636
UniProt	Q9HAB8	Q8VDG5
RefSeq (mRNA)	NM_001077447	NM_026494
RefSeq (protein)	NP_001070915	NP_080770
Location (UCSC)	Chr 1: 42.46 – 42.47 Mb	Chr 4: 119.42 – 119.42 Mb
PubMed search

Phosphopantothenoylcysteine synthetase in humans is encoded by the PPCS gene.^[2]

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. "Entrez Gene: Phosphopantothenoylcysteine synthetase".

Further reading

• Brown GM (1959). "The metabolism of pantothenic acid". J. Biol. Chem. 234 (2): 370–8. 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): 13513–6. 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): 36137–45. doi:10.1074/jbc.M206188200. PMID 12140293.