PROSITE documentation PDOC00012

Phosphopantetheine attachment site

Description

Phosphopantetheine (or pantetheine 4' phosphate) is the prosthetic group of acyl carrier proteins (ACP) in some multienzyme complexes where it serves as a 'swinging arm' for the attachment of activated fatty acid and amino-acid groups [1]. Phosphopantetheine is attached to a serine residue in these proteins [2]. ACP proteins or domains have been found in various enzyme systems which are listed below (references are only provided for recently determined sequences).

  • Fatty acid synthase (FAS), which catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. Bacterial and plant chloroplast FAS are composed of eight separate subunits which correspond to the different enzymatic activities; ACP is one of these polypeptides. Fungal FAS consists of two multifunctional proteins, FAS1 and FAS2; the ACP domain is located in the N-terminal section of FAS2. Vertebrate FAS consists of a single multifunctional enzyme; the ACP domain is located between the β-ketoacyl reductase domain and the C-terminal thioesterase domain [3].
  • Polyketide antibiotics synthase enzyme systems. Polyketides are secondary metabolites produced from simple fatty acids, by microorganisms and plants. ACP is one of the polypeptidic components involved in the biosynthesis of Streptomyces polyketide antibiotics actinorhodin, curamycin, granatacin, monensin, oxytetracycline and tetracenomycin C.
  • Bacillus subtilis putative polyketide synthases pksK, pksL and pksM which respectively contain three, five and one ACP domains.
  • The multifunctional 6-methysalicylic acid synthase (MSAS) from Penicillium patulum. This is a multifunctional enzyme involved in the biosynthesis of a polyketide antibiotic and which contains an ACP domain in the C-terminal extremity.
  • Multifunctional mycocerosic acid synthase (gene mas) from Mycobacterium bovis.
  • Gramicidin S synthase I (gene grsA) from Bacillus brevis. This enzyme catalyzes the first step in the biosynthesis of the cyclic antibiotic gramicidin S.
  • Tyrocidine synthase I (gene tycA) from Bacillus brevis. The reaction carried out by tycA is identical to that catalyzed by grsA.
  • Gramicidin S synthase II (gene grsB) from Bacillus brevis. This enzyme is a multifunctional protein that activates and polymerizes proline, valine, ornithine and leucine. GrsB contains four ACP domains.
  • Erythronolide synthase proteins 1, 2 and 3 from Saccharopolyspora erythraea which is involved in the biosynthesis of the polyketide antibiotic erythromicin. Each of these proteins contain two ACP domains.
  • Conidial green pigment synthase from Aspergillus nidulans.
  • ACV synthase from various fungi. This enzyme catalyzes the first step in the biosynthesis of penicillin and cephalosporin. It contains three ACP domains.
  • Enterobactin synthase component F (gene entF) from Escherichia coli. This enzyme is involved in the ATP-dependent activation of serine during enterobactin (enterochelin) biosynthesis.
  • Cyclic peptide antibiotic surfactin synthase subunits 1, 2 and 3 from Bacillus subtilis. Subunits 1 and 2 contains three related domains while subunit 3 only contains a single domain.
  • HC-toxin synthase (gene HTS1) from Cochliobolus carbonum. This enzyme synthesizes HC-toxin, a cyclic tetrapeptide. HTS1 contains four ACP domains.
  • Fungal mitochondrial ACP, which is part of the respiratory chain NADH dehydrogenase (complex I).
  • Rhizobium nodulation protein nodF, which probably acts as an ACP in the synthesis of the nodulation Nod factor fatty acyl chain.

The sequence around the phosphopantetheine attachment site is conserved in all these proteins and can be used as a signature pattern. A profile was also developed that spans the complete ACP-like domain.

Last update:

December 2004 / Pattern and text revised.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

ACP_DOMAIN, PS50075; Acyl carrier protein phosphopantetheine domain profile  (MATRIX)
Sequences known to belong to this class detected by the profile: ALL
Other sequence(s) detected in Swiss-Prot: NONE.
• Domain architecture view of Swiss-Prot proteins matching PS50075
PS50075
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50075
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50075
• Scan Swiss-Prot/TrEMBL entries against PS50075
• view ligand binding statistics
Matching PDB structures: 1ACP 1AF8 1DNY 1DV5 ... [ALL]
PHOSPHOPANTETHEINE, PS00012; Phosphopantetheine attachment site  (PATTERN)
Consensus pattern: [DEQGSTALMKRH]-[LIVMFYSTAC]-[GNQ]-[LIVMFYAG]-[DNEKHS]-S-[LIVMST]-{PCFY}-[STAGCPQLIVMF]-[LIVMATN]-[DENQGTAKRHLM]-[LIVMWSTA]-[LIVGSTACR]-{LPIY}-{VY}-[LIVMFA]
S is the pantetheine attachment site
Sequences known to belong to this class detected by the pattern: ALL, except C.paradoxa ACP
Other sequence(s) detected in Swiss-Prot: 115.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00012
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00012
• Scan Swiss-Prot/TrEMBL entries against PS00012
• view ligand binding statistics
Matching PDB structures: 1ACP 1AF8 1DNY 1HY8 ... [ALL]

References

1
Source Concise Encyclopedia Biochemistry, Second Edition, Walter de Gruyter, Berlin New-York (1988).
2 Authors Pugh E.L., Wakil S.J.
Source J. Biol. Chem. 240:4727-4733(1965).
3 Authors Witkowski A., Rangan V.S., Randhawa Z.I., Amy C.M., Smith S.
Title Structural organization of the multifunctional animal fatty-acid synthase.
Source Eur. J. Biochem. 198:571-579(1991).
PubMed ID 2050137

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