Essential dynamics and sidechain hydrogen bond cluster studies on eosinophil cationic protein

Sanjeev, B. S.; Vishveshwara, S.

doi:10.1140/epjd/e2002-00151-x

Cited by 10 publications

(11 citation statements)

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“…However, only a restricted set have been subjected to dynamic investigation, considerably restricting flexibility comparisons between evolutionarily diverse enzymes with this structural fold. Although this is not an entirely comprehensive list, experimental and/or theoretical dynamic studies have been performed on free, ligand‐bound, wild‐type and/or mutant forms of human and rat RNase 1 , human eosinophil‐derived neurotoxin (EDN, or RNase 2) , human ECP (or RNase 3) , human RNase 4 , bovine and human angiogenin (hANG, RNase 5) , the northern leopard frog ranpirnase (Onconase) , and monomeric derivatives of bovine seminal RNase (BS‐RNase) . The details of some of these dynamic studies will now be briefly described and compared with the local and global motional behavior of RNase A.…”

Section: Conserved Functional Motions Among Structural Homologsmentioning

confidence: 99%

Structural and functional importance of local and global conformational fluctuations in the RNase A superfamily

Gagné

Doucet

2013

The FEBS Journal

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Understanding the relationship between protein structure and flexibility is of utmost importance for deciphering the tremendous rates of reactions catalyzed by enzyme biocatalysts. It has been postulated that protein homologs have evolved similar dynamic fluctuations to promote catalytic function, a property that would presumably be encoded in their structural fold. Using one of the best-characterized enzyme systems of the past century, we explore this hypothesis by comparing the numerous and diverse flexibility reports available for a number of structural and functional homologs of the pancreatic-like RNase A superfamily. Using examples from the literature and from our own work, we cover recent and historical evidence pertaining to the highly dynamic nature of this important structural fold, as well as the presumed importance of local and global concerted motions on the ribonucleolytic function. This minireview does not pretend to cover the overwhelming RNase A literature in a comprehensive manner; rather, efforts have been made to focus on the characterization of multiple timescale motions observed in the free and/or ligand-bound structural homologs as they proceed along the reaction coordinates. Although each characterized enzyme of this architectural fold shows unique motional features on a local scale, accumulating evidence from X-ray crystallography, NMR spectroscopy and molecular dynamics simulations suggests that global dynamic fluctuations, such as the functionally relevant hinge-bending motion observed in the prototypical RNase A, are shared between homologs of the pancreatic-like RNase superfamily. These observations support the hypothesis that analogous dynamic residue clusters are evolutionarily conserved among structural and functional homologs catalyzing similar enzymatic reactions.

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Section: Conserved Functional Motions Among Structural Homologsmentioning

confidence: 99%

Structural and functional importance of local and global conformational fluctuations in the RNase A superfamily

Gagné

Doucet

2013

The FEBS Journal

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“…S9 ). It is worth noting that the role of hydrogen bonds in terms of folding and stability of proteins does not necessarily lead to any ordered structural classification and thus a systematic investigation could be difficult ( Sanjeev & Vishveshwara, 2002 ). The analysed hydrogen bonds revealed differences between the numbers of additional hydrogen bonds in all solvents.…”

Section: Resultsmentioning

confidence: 99%

Lid opening and conformational stability of T1 Lipase is mediated by increasing chain length polar solvents

Maiangwa

Ali

Salleh

et al. 2017

PeerJ

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The dynamics and conformational landscape of proteins in organic solvents are events of potential interest in nonaqueous process catalysis. Conformational changes, folding transitions, and stability often correspond to structural rearrangements that alter contacts between solvent molecules and amino acid residues. However, in nonaqueous enzymology, organic solvents limit stability and further application of proteins. In the present study, molecular dynamics (MD) of a thermostable Geobacillus zalihae T1 lipase was performed in different chain length polar organic solvents (methanol, ethanol, propanol, butanol, and pentanol) and water mixture systems to a concentration of 50%. On the basis of the MD results, the structural deviations of the backbone atoms elucidated the dynamic effects of water/organic solvent mixtures on the equilibrium state of the protein simulations in decreasing solvent polarity. The results show that the solvent mixture gives rise to deviations in enzyme structure from the native one simulated in water. The drop in the flexibility in H2O, MtOH, EtOH and PrOH simulation mixtures shows that greater motions of residues were influenced in BtOH and PtOH simulation mixtures. Comparing the root mean square fluctuations value with the accessible solvent area (SASA) for every residue showed an almost correspondingly high SASA value of residues to high flexibility and low SASA value to low flexibility. The study further revealed that the organic solvents influenced the formation of more hydrogen bonds in MtOH, EtOH and PrOH and thus, it is assumed that increased intraprotein hydrogen bonding is ultimately correlated to the stability of the protein. However, the solvent accessibility analysis showed that in all solvent systems, hydrophobic residues were exposed and polar residues tended to be buried away from the solvent. Distance variation of the tetrahedral intermediate packing of the active pocket was not conserved in organic solvent systems, which could lead to weaknesses in the catalytic H-bond network and most likely a drop in catalytic activity. The conformational variation of the lid domain caused by the solvent molecules influenced its gradual opening. Formation of additional hydrogen bonds and hydrophobic interactions indicates that the contribution of the cooperative network of interactions could retain the stability of the protein in some solvent systems. Time-correlated atomic motions were used to characterize the correlations between the motions of the atoms from atomic coordinates. The resulting cross-correlation map revealed that the organic solvent mixtures performed functional, concerted, correlated motions in regions of residues of the lid domain to other residues. These observations suggest that varying lengths of polar organic solvents play a significant role in introducing dynamic conformational diversity in proteins in a decreasing order of polarity.

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“…Interestingly, the networks of the intrachain type were similarly located in both chains. For instance, the networks 1A and 1B connected the residues Asn 27 and Tyr…”

Section: Correlation Between Maximum Residencementioning

confidence: 99%

“…An established method to identify −essential× subspace from protein dynamics has been provided by Amadei et al [26]. The method, as applied to the present work, has been discussed by Sanjeev and Vishveshwara [27].…”

Section: Experimental Partmentioning

confidence: 99%

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Stability and Dynamics of Domain‐Swapped Bovine‐Seminal Ribonuclease

Chakrabarti¹,

Sanjeev²,

Vishveshwara³

2004

Chemistry & Biodiversity

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The proteins of the ribonuclease-A (RNase-A) family are monomeric, with the exception of bovine-seminal ribonuclease (BS-RNase). BS-RNase is formed by swapping the N-terminal helices across the two monomeric units. A molecular-dynamics (MD) study has been performed on the protein for a simulation time of 5.5 ns to understand the factors responsible for the stability of the dimer. Essential dynamics analysis and motional correlation of the protein atoms yielded the picture of a stabilising, yet flexible, interface. We have investigated the role of intermolecular H-bonding, protein/water interaction, and protein/water networks in stabilising the dimer. The networks of interchain H-bonds involving side-chain/side-chain or side-chain/main-chain (ScHB) interactions between the two chains have also been studied. The ability of protein atoms in retaining particular H2O molecules was investigated as a function of the accessible surface area (ASA), depth, and hydration parameters, as well as their participation in protein/water networks.

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Essential dynamics and sidechain hydrogen bond cluster studies on eosinophil cationic protein

Cited by 10 publications

References 1 publication

Structural and functional importance of local and global conformational fluctuations in the RNase A superfamily

Structural and functional importance of local and global conformational fluctuations in the RNase A superfamily

Lid opening and conformational stability of T1 Lipase is mediated by increasing chain length polar solvents

Stability and Dynamics of Domain‐Swapped Bovine‐Seminal Ribonuclease

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