Dynamics based clustering of globin family members

Tobi, Dror

doi:10.1371/journal.pone.0208465

Cited by 6 publications

(11 citation statements)

References 77 publications

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“…The PDB file B-factor values are replaced by the RDSS and best dynamically matching areas are visualized by the B-factor coloring option of the used viewer, Pymol [54]. The ability of the current algorithm to identify local dynamics similarity is demonstrated in our recent papers, where we present a detailed dynamical comparison between myoglobin and hemoglobin [46] and show its ability to perform dynamics-based clustering [55].…”

Section: Methodsmentioning

confidence: 99%

Dynamical comparison between Drosha and Dicer reveals functional motion similarities and dissimilarities

Aharoni

Tobi

2019

PLoS ONE

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Drosha and Dicer are RNase III family members of classes II and III, respectively, which play a major role in the maturation of micro-RNAs. The two proteins share similar domain arrangement and overall fold despite no apparent sequence homology. The overall structural and catalytic reaction similarity of both proteins, on the one hand, and differences in the substrate and its binding mechanisms, on the other, suggest that both proteins also share dynamic similarities and dissimilarities. Since dynamics is essential for protein function, a comparison at their dynamics level is fundamental for a complete understanding of the overall relations between these proteins. In this study, we present a dynamical comparison between human Drosha and Giardia Dicer. Gaussian Network Model and Anisotropic Network Model modes of motion of the proteins are calculated. Dynamical comparison is performed using global and local dynamic programming algorithms for aligning modes of motion. These algorithms were recently developed based on the commonly used Needleman-Wunsch and Smith-Waterman algorithms for global and local sequence alignment. The slowest mode of Drosha is different from that of Dicer due to its more bended posture and allow the motion of the double-stranded RNA-binding domain toward and away from its substrate. Among the five slowest modes dynamics similarity exists only for the second slow mode of motion of Drosha and Dicer. In addition, high local dynamics similarity is observed at the catalytic domains, in the vicinity of the catalytic residues. The results suggest that the proteins exert a similar catalytic mechanism using similar motions, especially at the catalytic sites.

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Section: Methodsmentioning

confidence: 99%

Dynamical comparison between Drosha and Dicer reveals functional motion similarities and dissimilarities

Aharoni

Tobi

2019

PLoS ONE

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“…It is noteworthy that the elastic network approach does not require molecular dynamics but rather relies on a static structure and spring force constants derived empirically from a database of crystallographic B-factors. This instrument is well suited to exploring force propagation in biomolecules and had been used to address the properties of a variety of systems such as cooperativity in protein dimers and tetramers, 49,50 signal transduction in ion channels, 51 and transcription factors bound to their DNA targets. 52 Naked 12-mer DNA (PDB entry 355D 53 ) demonstrated good correlations of vibrational movements propagating along each strand for approximately two or three nucleotides except for the terminal parts (Figure S1).…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Critical Sites of DNA Backbone Integrity for Damaged Base Removal by Formamidopyrimidine–DNA Glycosylase

Endutkin

Zharkov

2019

Biochemistry

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DNA glycosylases, the enzymes that initiate base excision DNA repair, recognize damaged bases through a series of precisely orchestrated movements. Most glycosylases sharply kink the DNA axis at the lesion site and extrude the target base from the DNA double helix into the enzyme's active site. Little attention has been paid so far to the role of the physical continuity of the DNA backbone in allowing the required conformational distortion. Here, we analyze base excision by formamidopyrimidine−DNA glycosylase (Fpg) from substrates keeping all phosphates but containing a nick within three nucleotides of the lesion in either DNA strand. Four phosphoester linkages at the damaged nucleotide and two nucleotides 3′ to it were essential for Fpg activity, while the breakage of the others, even at the same critical phosphates, had no effect or even stimulated the reaction. Reduction of the likelihood of hydrogen bonding at the nicks by using dideoxynucleotides as their 3′-terminal groups was more detrimental for the activity. All phosphoester bonds in the complementary strand were dispensable for base excision, but nicks close to the orphaned nucleotide caused early termination of damaged strand cleavage. Elastic network analysis of Fpg−DNA structures showed that the vibrational motions of the critical phosphates are strongly correlated, in part due to the presence of the protein. Overall, our results suggest that mechanical forces propagating along the DNA backbone play a critical role in the correct conformational distortion of DNA by Fpg and possibly by other target base-everting DNA glycosylases.

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“…24 Still aiming at a protein family, Tobi developed an ENM-based method to make a function classification for globin family members based on their dynamics' similarity. 25 Besides, in 2020, an insightful review by Bahar et al revealed the evolutionary constraints on structure dynamics of a protein family to achieve the required functions: the slowest motion modes are conserved by a protein family for the common function; the low-to-intermediate frequency (LTIF) modes reflect the function specificity across family members; the fastest frequency modes ensure the core stability, which is the basics of functional specialization. 26 Besides the ENM model, currently, the protein structure network (PSN) has been widely used in the studies of protein folding, allosteric transition, and key site prediction.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Combined with the ENM model, perturbation response scanning (PRS) analysis was proposed to obtain protein dynamics and allosteric properties, and currently, the method has been widely applied to identify the key residues in allosteric control and long-range communications for large protein assemblies. , Additionally, a systematic method of approach was developed by Bahar et al for characterizing the shared (signature) as well as unique structural and dynamic properties of a protein family using a combination of structure-based models and methods . Still aiming at a protein family, Tobi developed an ENM-based method to make a function classification for globin family members based on their dynamics’ similarity . Besides, in 2020, an insightful review by Bahar et al revealed the evolutionary constraints on structure dynamics of a protein family to achieve the required functions: the slowest motion modes are conserved by a protein family for the common function; the low-to-intermediate frequency (LTIF) modes reflect the function specificity across family members; the fastest frequency modes ensure the core stability, which is the basics of functional specialization …”

Section: Introductionmentioning

confidence: 99%

Insight into Shared Properties and Differential Dynamics and Specificity of Secretory Phospholipase A₂ Family Members

et al. 2021

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Understanding generic mechanisms of functions shared by the secretory phospholipase A 2 (sPLA 2 ) family involved in the lipid metabolism and cell signaling and the molecular basis of function specificity for family members is an intriguing but challenging problem for biologists. Here, we explore the issue through extensive analyses using a combination of structure-based methods and bioinformatics tools on130 sPLA 2 family members. The principal component analysis of the structure ensemble reveals that the enzyme has an open−close motion which helps widen the substrate binding channel, facilitating its binding to phospholipid. Performing elastic network model and sequence analyses found that the residues critical for family functions, such as cysteine and catalytic residues, are highly conserved and undergo minimal movements, which is evolutionarily essential as their perturbation would impact the function, while the four residue regions involved in the association with the calcium ion/membrane are lowly conserved and of high mobility and large variations in low-to-intermediate frequency modes, which reflects the specificity of members. The analyses from perturbation response scanning also reveal that the above four regions with high sensitivity to an external perturbation are member-specific, suggesting their different roles in allosteric modulation, while the minimal sensitive residues are the shared characteristics across family members, which play an important role in maintaining structural stability as the folding core. This study is helpful for understanding how sequences, structures, and dynamics of sPLA 2 family members evolve to ensure their common and specific functions and can provide a guide for accurate design of proteins with finely tuned activities.

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Dynamics based clustering of globin family members

Cited by 6 publications

References 77 publications

Dynamical comparison between Drosha and Dicer reveals functional motion similarities and dissimilarities

Dynamical comparison between Drosha and Dicer reveals functional motion similarities and dissimilarities

Critical Sites of DNA Backbone Integrity for Damaged Base Removal by Formamidopyrimidine–DNA Glycosylase

Insight into Shared Properties and Differential Dynamics and Specificity of Secretory Phospholipase A₂ Family Members

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Dynamics based clustering of globin family members

Cited by 6 publications

References 77 publications

Dynamical comparison between Drosha and Dicer reveals functional motion similarities and dissimilarities

Dynamical comparison between Drosha and Dicer reveals functional motion similarities and dissimilarities

Critical Sites of DNA Backbone Integrity for Damaged Base Removal by Formamidopyrimidine–DNA Glycosylase

Insight into Shared Properties and Differential Dynamics and Specificity of Secretory Phospholipase A2 Family Members

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Insight into Shared Properties and Differential Dynamics and Specificity of Secretory Phospholipase A₂ Family Members