Structure and dynamics of human and bacterial acyl carrier proteins and their interactions with fatty acid synthesis proteins

Park, Jungwoo; Lee, Yeongjoon; Cheon, Dasom; Kim, Yangmee

doi:10.1016/j.bbrc.2019.07.018

Cited by 3 publications

(4 citation statements)

References 28 publications

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“…In most type I systems, no interaction was observed between the ACP and its Ppant arm or acyl chain, suggesting that substrate sequestration does not occur in type I ACPs [21,22,30,35,41–48] . The entrance to the hydrophobic cavity seems to be blocked by a hydrophobic triad (Leu2144, Leu2149, Val2174 in rat FAS, PDB ID: 2PNG, [22] UniProt: P12785), which is not found in type II ACPs (Figure 4B).…”

Section: Acp Structure and Cargo Transportmentioning

confidence: 98%

“…[38] In most type I systems, no interaction was observed between the ACP and its Ppant arm or acyl chain, suggesting that substrate sequestration does not occur in type I ACPs. [21,22,30,35,[41][42][43][44][45][46][47][48] The entrance to the hydrophobic cavity seems to be blocked by a hydrophobic triad (Leu2144, Leu2149, Val2174 in rat FAS, PDB ID: 2PNG, [22] UniProt: P12785), which is not found in type II ACPs (Figure 4B). [21,22,42] MD simulations in rat FAS showed further blocking of the cavity by the highly conserved residue Arg2172 (Figure 3C), which is not found in type II ACPs.…”

Section: Acp Structure and Cargo Transportmentioning

confidence: 99%

See 1 more Smart Citation

How Acyl Carrier Proteins (ACPs) Direct Fatty Acid and Polyketide Biosynthesis

Buyachuihan,

Stegemann,

Grininger

2023

Angew Chem Int Ed

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Megasynthases, such as type I fatty acid and polyketide synthases (FASs and PKSs), are multienzyme complexes responsible for producing primary metabolites and complex natural products. Fatty acids (FAs) and polyketides (PKs) are built by assembling and modifying small acyl moieties in a stepwise manner. A central aspect of FA and PK biosynthesis involves the shuttling of substrates between the domains of the multienzyme complex. This essential process is mediated by small acyl carrier proteins (ACPs). The ACPs must navigate to the different catalytic domains within the multienzyme complex in a particular order to guarantee the fidelity of the biosynthesis pathway. However, the precise mechanisms underlying ACP‐mediated substrate shuttling, particularly the factors contributing to the programming of the ACP movement, still need to be fully understood. This review illustrates the current understanding of substrate shuttling, including concepts of conformational and specificity control, and proposes a confined ACP movement within type I megasynthases.

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Section: Acp Structure and Cargo Transportmentioning

confidence: 98%

Section: Acp Structure and Cargo Transportmentioning

confidence: 99%

How Acyl Carrier Proteins (ACPs) Direct Fatty Acid and Polyketide Biosynthesis

Buyachuihan,

Stegemann,

Grininger

2023

Angew Chem Int Ed

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show abstract

“…In den meisten Typ I Systemen wurden keine Wechselwirkungen zwischen dem ACP und seinem Ppant‐Arm oder der Acylkette beobachtet, was darauf hinweist, dass eine Substratsequestrierung bei Typ I ACPs nicht stattfindet [21,22,30,35,41–48] . Der Zugang zur hydrophoben Tasche scheint durch eine hydrophobe Triade (Leu2144, Leu2149, Val2174 in Ratten‐FAS, PDB ID: 2PNG, [22] UniProt: P12785) blockiert zu sein, die in ACPs vom Typ II nicht vorkommt (Abbildung 4B).…”

Section: Acp‐struktur Und Ladungstransportunclassified

“…[38] In den meisten Typ I Systemen wurden keine Wechselwirkungen zwischen dem ACP und seinem Ppant-Arm oder der Acylkette beobachtet, was darauf hinweist, dass eine Substratsequestrierung bei Typ I ACPs nicht stattfindet. [21,22,30,35,[41][42][43][44][45][46][47][48] Der Zugang zur hydrophoben Tasche scheint durch eine hydrophobe Triade (Leu2144, Leu2149, Val2174 in Ratten-FAS, PDB ID: 2PNG, [22] UniProt: P12785) blockiert zu sein, die in ACPs vom Typ II nicht vorkommt (Abbildung 4B). [21,22,42] MD-Simulationen des Ratten-FAS ACPs zeigen eine weitere Blockierung der Bindetasche durch die hochkonservierte Aminosäure Arg2172 (Abbildung 3C), die in Typ II ACPs nicht vorkommt.…”

Section: Acp-struktur Und Ladungstransportunclassified

Wie Acyl‐Carrier‐Proteine (ACPs) die Biosynthese von Fettsäuren und Polyketiden steuern

Buyachuihan,

Stegemann,

Grininger

2023

Angewandte Chemie

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Deciphering the Binding Interactions between Acinetobacter baumannii ACP and β-ketoacyl ACP Synthase III to Improve Antibiotic Targeting Using NMR Spectroscopy

Choi

Park

Yeon

et al. 2021

IJMS

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Fatty acid synthesis is essential for bacterial viability. Thus, fatty acid synthases (FASs) represent effective targets for antibiotics. Nevertheless, multidrug-resistant bacteria, including the human opportunistic bacteria, Acinetobacter baumannii, are emerging threats. Meanwhile, the FAS pathway of A. baumannii is relatively unexplored. Considering that acyl carrier protein (ACP) has an important role in the delivery of fatty acyl intermediates to other FAS enzymes, we elucidated the solution structure of A. baumannii ACP (AbACP) and, using NMR spectroscopy, investigated its interactions with β-ketoacyl ACP synthase III (AbKAS III), which initiates fatty acid elongation. The results show that AbACP comprises four helices, while Ca2+ reduces the electrostatic repulsion between acid residues, and the unconserved F47 plays a key role in thermal stability. Moreover, AbACP exhibits flexibility near the hydrophobic cavity entrance from D59 to T65, as well as in the α1α2 loop region. Further, F29 and A69 participate in slow exchanges, which may be related to shuttling of the growing acyl chain. Additionally, electrostatic interactions occur between the α2 and α3-helix of ACP and AbKAS III, while the hydrophobic interactions through the ACP α2-helix are seemingly important. Our study provides insights for development of potent antibiotics capable of inhibiting A. baumannii FAS protein–protein interactions.

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Structure and dynamics of human and bacterial acyl carrier proteins and their interactions with fatty acid synthesis proteins

Cited by 3 publications

References 28 publications

How Acyl Carrier Proteins (ACPs) Direct Fatty Acid and Polyketide Biosynthesis

How Acyl Carrier Proteins (ACPs) Direct Fatty Acid and Polyketide Biosynthesis

Wie Acyl‐Carrier‐Proteine (ACPs) die Biosynthese von Fettsäuren und Polyketiden steuern

Deciphering the Binding Interactions between Acinetobacter baumannii ACP and β-ketoacyl ACP Synthase III to Improve Antibiotic Targeting Using NMR Spectroscopy

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