Structural study of acyl carrier protein of Enterococcus faecalis and its interaction with enzymes in de novo fatty acid synthesis

Yeon, Jiwon; Oh, Sujung; Hwang, Eunha; Kim, Eun‐Hee; Kim, Yangmee

doi:10.1016/j.bbrc.2022.11.023

Cited by 3 publications

(8 citation statements)

References 43 publications

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“…Fig. 1B shows the hydrophobic interactions between these isoleucine residues and other residue forming the hydrophobic cavity of EfAcpA and EfAcpB, which accommodates growing acyl chains [ 13 , 14 ].…”

Section: Resultsmentioning

confidence: 99%

“…Higly conserved Ile, which are important for protein folding, are marked by a green box. ( B ) Solution structure of EfAcpA (PDB ID: 8GSA) and EfAcpB (PDB ID: 2N50) [ 13 , 14 ]. Conserved Ile residues are marked in red while hydrophobic residues are shown in yellow.…”

Section: Figmentioning

confidence: 99%

“…In our previous studies, we determined the solution structures of EfAcpA and EfAcpB using NMR spectroscopy [ 13 , 14 ]. We found that EfAcpB has three helices and one short helix III while EfAcpA has only three helices with a long α2α3 loop without short helix.…”

Section: Introductionmentioning

confidence: 99%

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Important Features for Protein Foldings in Two Acyl Carrier Proteins from Enterococcus faecalis

Yoo,

Yeon,

Kim

et al. 2023

J. Microbiol. Biotechnol.

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The emergence of multi-drug resistant Enterococcus faecalis raises a serious threat to global public health. E. faecalis is a gram-positive intestinal commensal bacterium found in humans. E. faecalis can endure extreme environments such as high temperature, pressure, and high salt, which facilitates them to cause infection in hospitals. E. faecalis has two acyl carrier proteins, AcpA (EfAcpA) in de novo fatty acid synthesis (FAS) and AcpB (EfAcpB) which utilizes exogenous fatty acids. Previously, we determined the tertiary structures of these two ACPs and investigated their structure-function relationships. Solution structures revealed that overall folding of these two ACPs is similar to those of other bacterial ACPs. However, circular dichroism (CD) experiments showed that the melting temperature of EfAcpA is 76.3°C and that of EfAcpB is 79.2°C, which are much higher than those of other bacterial ACPs. In this study, to understand the origin of their structural stabilities, we verified the important residues for stable folding of these two ACPs by monitoring thermal and chemical denaturation. Hydrogen/deuterium exchange and chemical denaturation experiments on wild-type and mutant proteins revealed that Ile10 of EfAcpA and Ile14 of EfAcpB mediate compact intramolecular packing and promote high thermostability and stable folding. E. faecalis may maximize efficiency of FAS and increase adaptability to the environmental stress by having two thermostable ACPs. This study may provide insight into bacterial adaptability and development of antibiotics against multi-drug-resistant E. faecalis .

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Section: Resultsmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

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Important Features for Protein Foldings in Two Acyl Carrier Proteins from Enterococcus faecalis

Yoo,

Yeon,

Kim

et al. 2023

J. Microbiol. Biotechnol.

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“…To address the emergence of antibiotic resistance in E. faecalis, we previously determined the solution structures of two E. faecalis ACPs using NMR spectroscopy. E. faecalis AcpA (EfAcpA) is an essential cofactor in de novo FAS, whereas E. faecalis AcpB (EfAcpB) is an essential cofactor in FAS using external fatty acids (Park et al 2016;Yeon et al 2022). We found that these two ACPs exhibited differences in the presence of the α 3 helix: EfAcpA possessed only three helices and lacked α 3 , which was present in EfAcpB.…”

Section: Introductionmentioning

confidence: 93%

“…The structures of various type II ACPs isolated from different organisms have been extensively examined. The solution structures of ACPs from Escherichia coli, Bacillus subtilis, Mycobacterium tuberculosis, Vibrio harveyi, Helicobacter pylori, Borrelia burgdorferi, and Plasmodium falciparum have been elucidated using NMR spectroscopy (Barnwal et al 2011;Choi et al 2021;Holak et al 1988;Lee et al 2020;Park et al 2004Park et al , 2016Sharma et al 2006;Wong et al 2002;Wu et al 2009;Xu et al 2001;Yeon et al 2022). E. coli ACP (EcACP), an extensively studied bacterial ACP (Kim and Prestegard 1989;Roujeinikova et al 2002), possesses two metal binding sites.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of acyl carrier protein in de novo fatty acid synthesis by Enterococcus faecalis based on NMR spectroscopy and molecular dynamics simulation

Oh,

Lee,

Son

et al. 2024

J Anal Sci Technol

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Fatty acid synthesis (FAS) is essential for the production of biological components such as cell membrane building blocks and metabolism-related compounds. There are two types of bacterial FAS: de novo FAS and FAS through the incorporation of external fatty acids. Enterococcus faecalis possesses two distinct acyl carrier proteins (ACPs), AcpA (EfAcpA) and AcpB (EfAcpB), which serve as cofactors in the two types of FAS. We previously showed through NMR spectroscopy that EfAcpA comprises only three long helices, while EfAcpB consists of four helices, including a short α3 helix, similar to other bacterial ACPs. An increase in melting temperature (Tm) from 64.0 to 76.1 °C confirmed that protein structural stability increased in the presence of calcium ions. Using NMR spectroscopy, two metal binding sites were identified in EfAcpA: site A was located at the start of the α2 helix while site B was situated near the α2 helix and α2α3 loop. To understand the importance of structural flexibility of EfAcpA in de novo FAS, we investigated its motional properties using backbone spin relaxation and molecular dynamics simulations. The α2α3 loop in EfAcpA displayed high flexibility, as indicated by low heteronuclear NOE values. The residues Val51, Glu54, and Gly58 exhibited significant R2 values, likely due to the movement of this loop. EfAcpA created a novel cavity towards the α1α2 loop, in contrast to conventional cavity formation in most bacterial ACPs. This unique behavior was attributed to the flexibility exhibited by the α2α3 loop. The structural and motional characteristics of EfAcpA confirmed that its conformational plasticity is a crucial factor influencing acyl chain transfers in de novo FAS. Given the increasing antibiotic resistance observed for E. faecalis in clinical settings, the findings of this study may contribute to the development of more effective pathogen management strategies targeting FAS.

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The acyl carrier proteins of lipid synthesis are busy having other affairs

Cronan

2023

Biochemical Journal

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This is a review of the acyl carrier proteins (ACPs) of type II fatty acid synthesis in bacteria and mitochondria, their structures and protein interactions. Type II fatty acid synthesis in bacteria (Prog. Lipid Res. (2013) 52, 249–276; Biochim. Biophys. Acta (1996) 1302, 1–16; Annu. Rev. Biochem. (2005) 74, 791–831) and in the mitochondria of yeast and mammals (Biochim. Biophys. Acta Mol. Cell. Res. (2019) 1866, 118540; MedChemComm (2019) 10, 209–220; Elife (2016) 5, e17828; Mol. Cell (2018) 71, 567–580.e4) will be discussed only tangentially in this review. The above references are excellent recent reviews. Bacterial fatty acid synthesis has been a popular target for the development of new antimicrobials and an up-to-date review of the field has been published (Annu. Rev. Microbiol. (2022) 76, 281–304). The ACP-like proteins of secondary metabolites (e.g. polyketide synthesis will not be reviewed). Escherichia coli ACP is now called AcpP to distinguish it from the enzymes that attach (AcpS) and remove (AcpH) the 4′-phosphopantetheine (4′PP) prosthetic group. Note that the primary translation product of the acpP gene is called apo-AcpP. The addition of the 4′PP prosthetic group converts apo-AcpP to holo-AcpP (commonly referred to as AcpP). Acylation of the 4′PP prosthetic group gives acyl-AcpP species. The length of the acyl chain determines the properties of the acyl-AcpP as will be discussed below.

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Structural study of acyl carrier protein of Enterococcus faecalis and its interaction with enzymes in de novo fatty acid synthesis

Cited by 3 publications

References 43 publications

Important Features for Protein Foldings in Two Acyl Carrier Proteins from Enterococcus faecalis

Important Features for Protein Foldings in Two Acyl Carrier Proteins from Enterococcus faecalis

Dynamics of acyl carrier protein in de novo fatty acid synthesis by Enterococcus faecalis based on NMR spectroscopy and molecular dynamics simulation

The acyl carrier proteins of lipid synthesis are busy having other affairs

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