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
⇌
{\displaystyle \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
1F7L ,
1F7T ,
1F80 ,
1FTE ,
1FTF ,
1FTH ,
2JBZ , and
2JCA .
References
^ 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.
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.
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 .
Activity Regulation Classification Kinetics Types