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- **************************************
- * Phosphopantetheine attachment site *
- **************************************
-
- 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 synthetase (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 beta-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
- the Streptomyces polyketide antibiotics granatacin [4] and tetracenomycin C
- [5].
- - The multifunctional 6-methysalicylic acid synthase (MSAS) from Penicillium
- patulum [6]. This is a multifunctional enzyme involved in the biosynthesis
- of a polyketide antibiotic and which contains an ACP domain in the C-
- terminal extremity.
- - The multifunctional mycocerosic acid synthase from Mycobacterium bovis [7].
- - Fungal mitochondrial ACP [8], 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.
-
- -Consensus pattern: [LIVY]-G-[LIVMFYAG]-[DK]-S-[LIVMT]-x(3)-[DET]-x(4)-[LIVMF]
- [S is the pantetheine attachment site]
- -Sequences known to belong to this class detected by the pattern: ALL, except
- for Anabaena variabilis ACP which has Gln in position 2 of the pattern.
- -Other sequence(s) detected in SWISS-PROT: phage lambda recombination protein
- bet and Listeria monocytogenes internalin A.
- -Last update: June 1994 / Pattern and text revised.
-
- [ 1] Concise Encyclopedia Biochemistry, Second Edition, Walter de Gruyter,
- Berlin New-York (1988).
- [ 2] Pugh E.L., Wakil S.J.
- J. Biol. Chem. 240:4727-4733(1965).
- [ 3] Witkowski A., Rangan V.S., Randhawa Z.I., Amy C.M., Smith S.
- Eur. J. Biochem. 198:571-579(1991).
- [ 4] Bibb M.J., Biro S., Motamedi H., Collins J.F., Hutchinson C.R.
- EMBO J. 8:2727-2736(1989).
- [ 5] Sherman D.H., Malpartida F., Bibb M.J., Kieser H.M., Bibb M.J.,
- Hopwood D.A.
- EMBO J. 8:2717-2725(1989).
- [ 6] Beck J., Ripka S., Siegner A., Schiltz E., Schweizer E.
- Eur. J. Biochem. 192:487-498(1990).
- [ 7] Mathur M., Kolattukudy P.E.
- J. Biol. Chem. 267:19388-19395(1992).
- [ 8] Sackmann U., Zensen R., Rohlen D., Jahnke U., Weiss H.
- Eur. J. Biochem. 200:463-469(1991).
-