Investigation of intrinsic dynamics of enzymes involved in metabolic pathways using coarse-grained normal mode analysis

Meeuwsen, Sarah M.; Hodac, An Nam; Adams, Lauren; McMunn, Ryan; Anschutz, Maxwell S.; Carothers, Kari J.; Egdorf, Rachel E.; Hanneman, Peter M.; Kitzrow, Jonathan; Keonigsberg, Cynthia K.; Lopez-Martinez, Oscar; Matthew, Paul A.; Richter, Ethan H.; Schenk, Jonathan E.; Schmit, Heidi L.; Scott, Matthew A.; Volenec, Eva M.; Hati, Sanchita

doi:10.1080/23312025.2017.1291877

Cited by 4 publications

(5 citation statements)

References 70 publications

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“…Single and comparative NMA analyses were performed using the WebNM@ server ([ 43 ] accessed October 2019). This tool is able to calculate the low-frequency normal modes by building the coarse-grained Elastic Network Model (ENM) of a submitted pdb file [ 44 , 45 ]. This way, the protein is represented as a string of beads of C α atoms, interacting following formula F a : where r i and r j are the positions of residues I and j in the current conformation of the protein, and the superscript 0 denotes the equilibrium conformation; k ij is the force constant for the spring connecting residues I and j.…”

Section: Methodsmentioning

confidence: 99%

“…This way, the protein is represented as a string of beads of C α atoms, interacting following formula F a : where r i and r j are the positions of residues I and j in the current conformation of the protein, and the superscript 0 denotes the equilibrium conformation; k ij is the force constant for the spring connecting residues I and j. In the single mode, this software calculates the dynamic cross-correlation matrices (DCCM) [ 44 ], which help to identify the correlated and anticorrelated motions [ 45 ]. The coupling between two C α atoms i and j in the DCCM is defined by formula F b : …”

Section: Methodsmentioning

confidence: 99%

Section: Single and Comparative Normal Modes Analysis (Nma)mentioning

confidence: 99%

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Normal modes analysis and surface electrostatics of haemagglutinin proteins as fingerprints for high pathogenic type A influenza viruses

Righetto

Filippini

2020

BMC Bioinformatics

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Background: Type A influenza viruses circulate and spread among wild birds and mostly consist of low pathogenic strains. However, fast genome variation timely results in the insurgence of high pathogenic strains, which when infecting poultry birds may cause a million deaths and strong commercial damage. More importantly, the host shift may concern these viruses and sustained human-to-human transmission may result in a dangerous pandemic outbreak. Therefore, fingerprints specific to either low or high pathogenic strains may represent a very important tool for global surveillance. Results: We combined Normal Modes Analysis and surface electrostatic analysis of a mixed strain dataset of influenza A virus haemagglutinins from high and low pathogenic strains in order to infer specific fingerprints. Normal Modes Analysis sorted the strains in two different, homogeneous clusters; sorting was independent of clades and specific instead to high vs low pathogenicity. A deeper analysis of fluctuations and flexibility regions unveiled a special role for the 110-helix region. Specific sorting was confirmed by surface electrostatics analysis, which further allowed to focus on regions and mechanisms possibly crucial to the low-to-high transition. Conclusions: Evidence from previous work demonstrated that changes in surface electrostatics are associated with the evolution and spreading of avian influenza A virus clades, and seemingly involved also in the avian to mammalian host shift. This work shows that a combination of electrostatics and Normal Modes Analysis can also identify fingerprints specific to high and low pathogenicity. The possibility to predict which specific mutations may result in a shift to high pathogenicity may help in surveillance and vaccine development.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Single and Comparative Normal Modes Analysis (Nma)mentioning

confidence: 99%

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Normal modes analysis and surface electrostatics of haemagglutinin proteins as fingerprints for high pathogenic type A influenza viruses

Righetto

Filippini

2020

BMC Bioinformatics

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“…In addition to electrostatics, we also took into account protein dynamics by performing Normal Modes Analysis (NMA) [31]. NMA allowed us to highlight further fingerprints for soluble vs. insoluble BVMOs.…”

Section: Normal Modes Analysis Of Htbvmo and Soluble/insoluble Enzymesmentioning

confidence: 99%

“…Single and comparative NMA analyses were performed using the WebNM@ server [32]. This tool is able to calculate the low-frequency normal modes by building the coarse-grained Elastic Network Model (ENM) of a submitted pdb file [31], returning the protein, represented as a string of beads of C α atoms. In this work, the default settings of WebNM@ were used.…”

Section: Single and Comparative Normal Mode Analysismentioning

confidence: 99%

Unique Features of a New Baeyer–Villiger Monooxygenase from a Halophilic Archaeon

et al. 2020

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Type I Baeyer–Villiger monooxygenases (BVMOs) are flavin-dependent monooxygenases that catalyze the oxidation of ketones to esters or lactones, a reaction otherwise performed in chemical processes by employing hazardous and toxic peracids. Even though various BVMOs are extensively studied for their promising role in industrial biotechnology, there is still a demand for enzymes that are able to retain activity at high saline concentrations. To this aim, and based on comparative in silico analyses, we cloned HtBVMO from the extremely halophilic archaeon Haloterrigena turkmenica DSM 5511. When expressed in standard mesophilic cell factories, proteins adapted to hypersaline environments often behave similarly to intrinsically disordered polypeptides. Nevertheless, we managed to express HtBVMO in Escherichia coli and could purify it as active enzyme. The enzyme was characterized in terms of its salt-dependent activity and resistance to some water–organic-solvent mixtures. Although HtBVMO does not seem suitable for industrial applications, it provides a peculiar example of an alkalophilic and halophilic BVMO characterized by an extremely negative charge. Insights into the behavior and structural properties of such salt-requiring may contribute to more efficient strategies for engineering the tuned stability and solubility of existing BVMOs.

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Integrating Research into the Curriculum: A Low-Cost Strategy for Promoting Undergraduate Research

Hati

Bhattacharyya

2018

ACS Symposium Series

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Investigation of intrinsic dynamics of enzymes involved in metabolic pathways using coarse-grained normal mode analysis

Cited by 4 publications

References 70 publications

Normal modes analysis and surface electrostatics of haemagglutinin proteins as fingerprints for high pathogenic type A influenza viruses

Normal modes analysis and surface electrostatics of haemagglutinin proteins as fingerprints for high pathogenic type A influenza viruses

Unique Features of a New Baeyer–Villiger Monooxygenase from a Halophilic Archaeon

Integrating Research into the Curriculum: A Low-Cost Strategy for Promoting Undergraduate Research

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