Holo-(acyl-carrier-protein) synthase
| phosphopantetheinyltransferase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 holo-[acyl-carrier-protein] synthase trimer, Helicobacter pylori | |||||||||
| Identifiers | |||||||||
| EC no. | 2.7.8.7 | ||||||||
| CAS no. | 37278-30-1 | ||||||||
| Databases | |||||||||
| BRENDA | enzyme data | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | enzyme entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| Rhea | reactions | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
| ACPS | |||||||
|---|---|---|---|---|---|---|---|
 crystal structure of the 4'-phosphopantetheinyl transferase sfp-coenzyme a complex | |||||||
| Identifiers | |||||||
| Symbol | ACPS | ||||||
| Pfam | PF01648 | ||||||
| InterPro | IPR008278 | ||||||
| SCOP2 | 1qr0 / SCOPe / SUPFAM | ||||||
| |||||||
In enzymology and molecular biology, a holo-[acyl-carrier-protein] synthase (ACPS, EC 2.7.8.7) is an enzyme that catalyzes the chemical reaction:
- CoA-[4'-phosphopantetheine] + apo-acyl carrier protein adenosine 3',5'-bisphosphate + holo-acyl carrier protein
This enzyme belongs to the family of transferases, specifically those transferring non-standard substituted phosphate groups, and more specifically to the 4'-phosphopantetheinyl transferases (PPTases) named after the group they transfer.
In mammals, this activity is performed by the PPTase, aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase (AASDHPPT), which acts in both the cytosol and mitochondria.[1] It acts on all substrates with an acyl carrier protein domain, which includes not only the "type II" mitochondrial ACP (NDUFAB1), but also the ACP part in "type I" proteins AASDH, ALDH1L1, ALDH1L2, and FASN. It also processes DHRS2, which does not have an ACP domain.[1][2]
Function
All ACPS enzymes known so far are evolutionally related to each other in a single superfamily of proteins. It transfers a 4'-phosphopantetheine (4'-PP) moiety from coenzyme A (CoA) to an invariant serine in an acyl carrier protein (ACP), a small protein responsible for acyl group activation in fatty acid biosynthesis. This post-translational modification renders holo-ACP capable of acyl group activation via thioesterification of the cysteamine thiol of 4'-PP.[3] This superfamily consists of two subtypes: the trimeric ACPS type such as E. coli ACPS and the monomeric Sfp (PCP-synthesizing) type such as B. subtilis SFP. Structures from both families are now known. The active site accommodates a magnesium ion. The most highly conserved regions of the protein are involved in binding the magnesium ion.[4][5]
Nomenclature
The systematic name of this enzyme class is CoA-[4'-phosphopantetheine]:apo-[acyl-carrier-protein] 4'-pantetheinephosphotransferase. Other names in common use, disregarding the synthetase/synthase spelling difference, include acyl carrier protein holoprotein synthetase, holo-ACP synthetase, coenzyme A:fatty acid synthetase apoenzyme 4'-phosphopantetheine, acyl carrier protein synthetase (ACPS), PPTase, acyl carrier protein synthase, P-pant transferase, and CoA:apo-[acyl-carrier-protein] pantetheinephosphotransferase.
Structural studies
As of late 2007, 8 structures have been solved for this class of enzymes, with PDB accession codes PDB: 1F7L, PDB: 1F7T, PDB: 1F80, PDB: 1FTE, PDB: 1FTF, PDB: 1FTH, PDB: 2JBZ, and PDB: 2JCA.
References
- 1 2 Norden, Pieter R.; Wedan, Riley J.; Preston, Samuel E. J.; Canfield, Morgan; Graber, Naomi; Longenecker, Jacob Z.; Pentecost, Olivia A.; McLaughlin, Elizabeth; Hart, Madeleine L. (2024-05-10). "Mitochondrial Phosphopantetheinylation is Required for Oxidative Function". bioRxiv 10.1101/2024.05.09.592977.
- ↑ Chen, Nan; Liu, Yuan; Li, Yuanpei; Wang, Chu (7 September 2020). "Chemical Proteomic Profiling of Protein 4′‐Phosphopantetheinylation in Mammalian Cells". Angewandte Chemie International Edition. 59 (37): 16069–16075. doi:10.1002/anie.202004105.
- ↑ Lambalot RH, Walsh CT (October 1995). "Cloning, overproduction, and characterization of the Escherichia coli holo-acyl carrier protein synthase". The Journal of Biological Chemistry. 270 (42): 24658–61. doi:10.1074/jbc.270.42.24658. PMID 7559576.
- ↑ Reuter K, Mofid MR, Marahiel MA, Ficner R (December 1999). "Crystal structure of the surfactin synthetase-activating enzyme sfp: a prototype of the 4'-phosphopantetheinyl transferase superfamily". The EMBO Journal. 18 (23): 6823–31. doi:10.1093/emboj/18.23.6823. PMC 1171745. PMID 10581256.
- ↑ Marcella AM, Culbertson SJ, Shogren-Knaak MA, Barb AW (24 November 2017). "Structure, High Affinity, and Negative Cooperativity of the Escherichia coli Holo-(Acyl Carrier Protein):Holo-(Acyl Carrier Protein) Synthase Complex". Journal of Molecular Biology. 429 (23): 3763–3775. doi:10.1016/j.jmb.2017.10.015. PMID 29054754.
Further reading
- Elovson J, Vagelos PR (July 1968). "Acyl carrier protein. X. Acyl carrier protein synthetase". The Journal of Biological Chemistry. 243 (13): 3603–11. doi:10.1016/S0021-9258(19)34183-3. PMID 4872726.
- Prescott DJ, Vagelos PR (1972). "Acyl carrier protein". Advances in Enzymology and Related Areas of Molecular Biology. Advances in Enzymology - and Related Areas of Molecular Biology. Vol. 36. pp. 269–311. doi:10.1002/9780470122815.ch8. ISBN 9780470122815. PMID 4561013.
- Lambalot RH, Gehring AM, Flugel RS, Zuber P, LaCelle M, Marahiel MA, Reid R, Khosla C, Walsh CT (November 1996). "A new enzyme superfamily - the phosphopantetheinyl transferases". Chemistry & Biology. 3 (11): 923–36. doi:10.1016/S1074-5521(96)90181-7. PMID 8939709.
- Walsh CT, Gehring AM, Weinreb PH, Quadri LE, Flugel RS (October 1997). "Post-translational modification of polyketide and nonribosomal peptide synthases". Current Opinion in Chemical Biology. 1 (3): 309–15. Bibcode:1997COCB....1..309W. doi:10.1016/S1367-5931(97)80067-1. PMID 9667867.
- Mootz HD, Finking R, Marahiel MA (October 2001). "4'-phosphopantetheine transfer in primary and secondary metabolism of Bacillus subtilis". The Journal of Biological Chemistry. 276 (40): 37289–98. Bibcode:2001JBiCh.27637289M. doi:10.1074/jbc.M103556200. PMID 11489886.
- Joshi AK, Zhang L, Rangan VS, Smith S (August 2003). "Cloning, expression, and characterization of a human 4'-phosphopantetheinyl transferase with broad substrate specificity". The Journal of Biological Chemistry. 278 (35): 33142–9. doi:10.1074/jbc.M305459200. PMID 12815048.