scholarly journals ACYL CARRIER PROTEIN, IV. THE IDENTIFICATION OF 4'-PHOSPHOPANTETHEINE AS THE PROSTHETIC GROUP OF THE ACYL CARRIER PROTEIN

1965 ◽  
Vol 53 (2) ◽  
pp. 410-417 ◽  
Author(s):  
P. W. Majerus ◽  
A. W. Alberts ◽  
P. R. Vagelos
Keyword(s):  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Prosthetic Group

scholarly journals Sticky swinging arm dynamics: studies of an acyl carrier protein domain from the mycolactone polyketide synthase

2016 ◽  
Vol 473 (8) ◽  
pp. 1097-1110 ◽  
Author(s):  
Steven Vance ◽  
Olga Tkachenko ◽  
Ben Thomas ◽  
Mona Bassuni ◽  
Hui Hong ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Acyl Carrier Protein ◽  
Protein Domain ◽  
Carrier Protein ◽  
Protein Surface ◽  
Prosthetic Group ◽  
Polyketide Biosynthesis ◽  
Covalently Linked

When covalently linked to an acyl carrier protein (ACP) and loaded with acyl substrate-mimics, some 4′-phosphopantetheine prosthetic group arms swing freely, whereas others stick to the protein surface, suggesting a possible mode of interaction with enzyme domains during polyketide biosynthesis.

Acyl carrier protein: structure–function relationships in a conserved multifunctional protein family

2007 ◽  
Vol 85 (6) ◽  
pp. 649-662 ◽  
Author(s):  
David M. Byers ◽  
Huansheng Gong
Keyword(s):  
Fatty Acid ◽  
Active Sites ◽  
Fatty Acid Synthase ◽  
Acyl Carrier Protein ◽  
Divalent Cations ◽  
Structural Features ◽  
Carrier Protein ◽  
Type I ◽  
Prosthetic Group

Acyl carrier protein (ACP) is a universal and highly conserved carrier of acyl intermediates during fatty acid synthesis. In yeast and mammals, ACP exists as a separate domain within a large multifunctional fatty acid synthase polyprotein (type I FAS), whereas it is a small monomeric protein in bacteria and plastids (type II FAS). Bacterial ACPs are also acyl donors for synthesis of a variety of products, including endotoxin and acylated homoserine lactones involved in quorum sensing; the distinct and essential nature of these processes in growth and pathogenesis make ACP-dependent enzymes attractive antimicrobial drug targets. Additionally, ACP homologues are key components in the production of secondary metabolites such as polyketides and nonribosomal peptides. Many ACPs exhibit characteristic structural features of natively unfolded proteins in vitro, with a dynamic and flexible conformation dominated by 3 parallel α helices that enclose the thioester-linked acyl group attached to a phosphopantetheine prosthetic group. ACP conformation may also be influenced by divalent cations and interaction with partner enzymes through its “recognition” helix II, properties that are key to its ability to alternately sequester acyl groups and deliver them to the active sites of ACP-dependent enzymes. This review highlights recent progress in defining how the structural features of ACP are related to its multiple carrier roles in fatty acid metabolism.

scholarly journals Divergent acyl carrier protein decouples mitochondrial Fe-S cluster biogenesis from fatty acid synthesis in malaria parasites

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Seyi Falekun ◽  
Jaime Sepulveda ◽  
Yasaman Jami-Alahmadi ◽  
Hahnbeom Park ◽  
James A Wohlschlegel ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acyl Carrier Protein ◽  
Acyl Chain ◽  
Acid Synthesis ◽  
Complex Iii ◽  
Carrier Protein ◽  
Prosthetic Group ◽  
Malaria Parasites ◽  
Mitochondrial Fatty Acid

Most eukaryotic cells retain a mitochondrial fatty acid synthesis (FASII) pathway whose acyl carrier protein (mACP) and 4-phosphopantetheine (Ppant) prosthetic group provide a soluble scaffold for acyl chain synthesis and biochemically couple FASII activity to mitochondrial electron transport chain (ETC) assembly and Fe-S cluster biogenesis. In contrast, the mitochondrion of Plasmodium falciparum malaria parasites lacks FASII enzymes yet curiously retains a divergent mACP lacking a Ppant group. We report that ligand-dependent knockdown of mACP is lethal to parasites, indicating an essential FASII-independent function. Decyl-ubiquinone rescues parasites temporarily from death, suggesting a dominant dysfunction of the mitochondrial ETC. Biochemical studies reveal that Plasmodium mACP binds and stabilizes the Isd11-Nfs1 complex required for Fe-S cluster biosynthesis, despite lacking the Ppant group required for this association in other eukaryotes, and knockdown of parasite mACP causes loss of Nfs1 and the Rieske Fe-S protein in ETC Complex III. This work reveals that Plasmodium parasites have evolved to decouple mitochondrial Fe-S cluster biogenesis from FASII activity, and this adaptation is a shared metabolic feature of other apicomplexan pathogens, including Toxoplasma and Babesia. This discovery unveils an evolutionary driving force to retain interaction of mitochondrial Fe-S cluster biogenesis with ACP independent of its eponymous function in FASII.

scholarly journals Antibacterial Activity of N-Pentylpantothenamide Is Due to Inhibition of Coenzyme A Synthesis

2010 ◽  
Vol 54 (3) ◽  
pp. 1374-1377 ◽  
Author(s):  
Jacob Thomas ◽  
John E. Cronan
Keyword(s):  
Antibacterial Activity ◽  
Growth Inhibition ◽  
Coenzyme A ◽  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Prosthetic Group ◽  
Protein Moiety

ABSTRACT Growth inhibition by the pantothenate analog N-pentylpantothenamide (N5-Pan) has been attributed to the accumulation of acyl carrier protein carrying a prosthetic group modified by incorporation of N5-Pan. This was attributed to an inability of the AcpH acyl carrier protein phosphodiesterase to cleave the N5-Pan-modified prosthetic group from the protein moiety. We report that AcpH readily removes the N5-Pan-modified prosthetic group both in vivo and in vitro and show that N5-Pan blocks coenzyme A synthesis.

scholarly journals Dissecting how modular polyketide synthase ketoreductases interact with acyl carrier protein-attached substrates

2017 ◽  
Vol 53 (83) ◽  
pp. 11457-11460 ◽  
Author(s):  
Luisa Moretto ◽  
Steven Vance ◽  
Brennan Heames ◽  
R. William Broadhurst
Keyword(s):  
Binding Site ◽  
Active Site ◽  
Polyketide Synthase ◽  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Prosthetic Group ◽  
Correct Orientation ◽  
Interaction Studies ◽  
Modular Polyketide Synthase

Interaction studies show that KR domains possess a generic binding site for ACP domains and provide evidence that the 5′-phosphopantetheine prosthetic group plays a key role in delivering acyl substrates to the active site in the correct orientation.

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