Crystal structure of Acetyl-CoA carboxylase (AccB) from Streptomyces antibioticus and insights into the substrate-binding through in silico mutagenesis and biophysical investigations

Ali, Imtiaz; Khan, Abbas; Zhang, Fa; Khan, Taimoor; Wei, Dong‐Qing; Zheng, Jianting

doi:10.1016/j.compbiomed.2022.105439

Cited by 4 publications

(13 citation statements)

References 46 publications

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“…With the three hydrophobic, six hydrogen-bonding contacts, and two salt bridges by D 179 , V 223 , S 343 , Q 346 , S 350 , and Q 514 residues were observed consistent with the previously published report. 17 The binding pattern of the wild type is given in Figure 1A. On the other hand, the binding pattern of S343A was observed to be comparable with the wild type.…”

Section: Binding Analysis Of Acetyl-coa With the Wild Type And Mutantsmentioning

confidence: 81%

“…Our group recently reported a crystal structure of acetyl-CoA carboxylase complex CT domain (AccB) and submitted it to protein databank (http://www.rcsb.org/) under accession ID 7W5U. 17 The primary structural coordinates of AccB were assessed for any deformities and prepared by using Chimera modeling software. 18 The structure was minimized using the conjugate gradient and steepest descent algorithms.…”

Section: Structure Retrieval and Preparationmentioning

confidence: 99%

“…The molecular docking of the wild type has been previously reported to have the docking of −8.59 kcal/mol. 17 On the other hand, for the three substitutions, that is, for the S343A, the docking score was calculated to be −8.93, −9.12, and −9.25 kcal/mol, respectively. This demonstrates that upon the substitutions, the binding affinity of acetyl-CoA for AccB is increased.…”

Section: Binding Analysis Of Acetyl-coa With the Wild Type And Mutantsmentioning

confidence: 99%

“…For instance, a loop movement and its flexibility have been reported to be linked with the acetyl-CoA tighter binding and movement in the cavity in AccB. 17 Hence, considering the importance of this approach, we also calculated the residue flexibility as the RMSF of the entire complexes and active site residues only. As given in Figure 4A, the RMSF follows a similar pattern for all the complexes, including the wild type and the three mutations.…”

Section: Residue Flexibility Assessment Of the Whole Protein And Acti...mentioning

confidence: 99%

“…16 Our group recently reported the crystal structure of acetyl-CoA carboxylase CT domain from S. antibioticus and the key hotspot residues, which are responsible for substrate specificity, fixation, and processing. 17 The current study aims to improve the substrate binding of AccB from S. antibioticus. Our findings suggest the best substitutes for increased specificity of acetyl-CoA.…”

Section: Introductionmentioning

confidence: 99%

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Improving the substrate binding of acetyl‐CoA carboxylase (AccB) from Streptomyces antibioticus through computational enzyme engineering

Ali,

Wei,

Khan

et al. 2024

Biotech and App Biochem

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Malonyl‐CoA serves as the main building block for the biosynthesis of many important polyketides, as well as fatty acid–derived compounds, such as biofuel. Escherichia coli, Corynebacterium gultamicum, and Saccharomyces cerevisiae have recently been engineered for the biosynthesis of such compounds. However, the developed processes and strains often have insufficient productivity. In the current study, we used enzyme‐engineering approach to improve the binding of acetyl‐CoA with ACC. We generated different mutations, and the impact was calculated, which reported that three mutations, that is, S343A, T347W, and S350W, significantly improve the substrate binding. Molecular docking investigation revealed an altered binding network compared to the wild type. In mutants, additional interactions stabilize the binding of the inner tail of acetyl‐CoA. Using molecular simulation, the stability, compactness, hydrogen bonding, and protein motions were estimated, revealing different dynamic properties owned by the mutants only but not by the wild type. The findings were further validated by using the binding‐free energy (BFE) method, which revealed these mutations as favorable substitutions. The total BFE was reported to be −52.66 ± 0.11 kcal/mol for the wild type, −55.87 ± 0.16 kcal/mol for the S343A mutant, −60.52 ± 0.25 kcal/mol for T347W mutant, and −59.64 ± 0.25 kcal/mol for the S350W mutant. This shows that the binding of the substrate is increased due to the induced mutations and strongly corroborates with the docking results. In sum, this study provides information regarding the essential hotspot residues for the substrate binding and can be used for application in industrial processes.

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Section: Binding Analysis Of Acetyl-coa With the Wild Type And Mutantsmentioning

confidence: 81%

Section: Structure Retrieval and Preparationmentioning

confidence: 99%

Section: Binding Analysis Of Acetyl-coa With the Wild Type And Mutantsmentioning

confidence: 99%

Section: Residue Flexibility Assessment Of the Whole Protein And Acti...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Improving the substrate binding of acetyl‐CoA carboxylase (AccB) from Streptomyces antibioticus through computational enzyme engineering

Ali,

Wei,

Khan

et al. 2024

Biotech and App Biochem

Self Cite

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Transcriptomic analysis of the antibacterial mechanism of ε‐polylysine‐functionalized magnetic composites against Alicyclobacillus acidoterrestris and its application in apple juice

Jia,

Cai,

Yue

et al. 2024

J Sci Food Agric

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BACKGROUNDAlicyclobacillus acidoterrestris is a common microorganism in fruit juice. It can produce off‐odor metabolites and has been considered to be an important factor in juice contamination. Thus, the development of new strategy for the control of A. acidoterrestris has important practical significance. The primary objective of this work was to assess the antibacterial performance of ε‐polylysine‐functionalized magnetic composites (Fe3O4@MoS2@PAA‐EPL) in apple juice and its effect on juice quality. Moreover, the molecular mechanism of Fe3O4@MoS2@PAA‐EPL against A. acidoterrestris was explored by RNA sequencing (RNA‐Seq).RESULTSExperimental results indicated that the synthesized composites possessed the ability to inhibit the viability of A. acidoterrestris vegetative cells and spores. Besides, investigation on the quality of apple juice incubated with Fe3O4@MoS2@PAA‐EPL implied that the fabricated composites displayed negligible adverse effects on juice quality. In addition, the results of RNA‐Seq demonstrated that 833 differentially expressed genes (DEGs) were identified in Fe3O4@MoS2@PAA‐EPL‐treated A. acidoterrestris, which were associated with translation, energy metabolism, amino acid metabolism, membrane transport and cell integrity.CONCLUSIONThese results suggested that the treatment of Fe3O4@MoS2@PAA‐EPL disrupted energy metabolism, repressed cell wall synthesis and caused membrane transport disorder of bacterial cells. This work provides novel insights into the molecular antibacterial mechanism for ε‐polylysine‐functionalized magnetic composites against A. acidoterrestris. © 2024 Society of Chemical Industry.

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Integrated multiple-omics reveals the regulatory mechanism underlying the effects of homologous Bacillus tequilensis (GCB-3) on growth performance of grass carp (Ctenopharyngodon idellus)

Wang,

Zhang,

Zhang

et al. 2024

Aquaculture Reports

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Crystal structure of Acetyl-CoA carboxylase (AccB) from Streptomyces antibioticus and insights into the substrate-binding through in silico mutagenesis and biophysical investigations

Cited by 4 publications

References 46 publications

Improving the substrate binding of acetyl‐CoA carboxylase (AccB) from Streptomyces antibioticus through computational enzyme engineering

Improving the substrate binding of acetyl‐CoA carboxylase (AccB) from Streptomyces antibioticus through computational enzyme engineering

Transcriptomic analysis of the antibacterial mechanism of ε‐polylysine‐functionalized magnetic composites against Alicyclobacillus acidoterrestris and its application in apple juice

Integrated multiple-omics reveals the regulatory mechanism underlying the effects of homologous Bacillus tequilensis (GCB-3) on growth performance of grass carp (Ctenopharyngodon idellus)

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