Holo-(acyl-carrier-protein) synthase explained

phosphopantetheinyltransferase
Ec Number:	2.7.8.7
Cas Number:	37278-30-1
Go Code:	0008897
Width:	270

Symbol:	ACPS
ACPS
Pfam:	PF01648
Interpro:	IPR008278
Scop:	1qr0

In enzymology and molecular biology, a holo-[acyl-carrier-protein] synthase (ACPS,) is an enzyme that catalyzes the chemical reaction:

\rightleftharpoons adenosine 3',5'-bisphosphate + holo-acyl carrier protein

This enzyme belongs to the family of transferases, specifically those transferring non-standard substituted phosphate groups. It is also known as 4'-phosphopantetheinyl transferase after the group it transfers.

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.^[1] 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.^{[2] [3]}

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,,,,,,, and .

Further reading

• Elovson J, Vagelos PR . Acyl carrier protein. X. Acyl carrier protein synthetase . The Journal of Biological Chemistry . 243 . 13 . 3603–11 . July 1968 . 10.1016/S0021-9258(19)34183-3 . 4872726 . free .
• Book: Prescott DJ, Vagelos PR . Advances in Enzymology and Related Areas of Molecular Biology . Acyl carrier protein . 36 . 269–311 . 1972 . 4561013 . 10.1002/9780470122815.ch8 . 9780470122815 . Advances in Enzymology - and Related Areas of Molecular Biology .
• Lambalot RH, Gehring AM, Flugel RS, Zuber P, LaCelle M, Marahiel MA, Reid R, Khosla C, Walsh CT . A new enzyme superfamily - the phosphopantetheinyl transferases . Chemistry & Biology . 3 . 11 . 923–36 . November 1996 . 8939709 . 10.1016/S1074-5521(96)90181-7 . free .
• Walsh CT, Gehring AM, Weinreb PH, Quadri LE, Flugel RS . Post-translational modification of polyketide and nonribosomal peptide synthases . Current Opinion in Chemical Biology . 1 . 3 . 309–15 . October 1997 . 9667867 . 10.1016/S1367-5931(97)80067-1 .
• Mootz HD, Finking R, Marahiel MA . 4'-phosphopantetheine transfer in primary and secondary metabolism of Bacillus subtilis . The Journal of Biological Chemistry . 276 . 40 . 37289–98 . October 2001 . 11489886 . 10.1074/jbc.M103556200 . free .
• Joshi AK, Zhang L, Rangan VS, Smith S . Cloning, expression, and characterization of a human 4'-phosphopantetheinyl transferase with broad substrate specificity . The Journal of Biological Chemistry . 278 . 35 . 33142–9 . August 2003 . 12815048 . 10.1074/jbc.M305459200 . free .

Notes and References

1. Lambalot RH, Walsh CT . Cloning, overproduction, and characterization of the Escherichia coli holo-acyl carrier protein synthase . The Journal of Biological Chemistry . 270 . 42 . 24658–61 . October 1995 . 7559576 . 10.1074/jbc.270.42.24658 . free .
2. Reuter K, Mofid MR, Marahiel MA, Ficner R . Crystal structure of the surfactin synthetase-activating enzyme sfp: a prototype of the 4'-phosphopantetheinyl transferase superfamily . The EMBO Journal . 18 . 23 . 6823–31 . December 1999 . 10581256 . 1171745 . 10.1093/emboj/18.23.6823 .
3. Marcella AM, Culbertson SJ, Shogren-Knaak MA, Barb AW. Structure, High Affinity, and Negative Cooperativity of the Escherichia coli Holo-(Acyl Carrier Protein):Holo-(Acyl Carrier Protein) Synthase Complex. . Journal of Molecular Biology . 24 November 2017 . 429 . 23 . 3763–3775 . 10.1016/j.jmb.2017.10.015 . 29054754. free .