scholarly journals Functional Group Introduction and Aromatic Unit Variation in a Set of π-Conjugated Macrocycles: Revealing the Central Role of Local and Global Aromaticity

2021 ◽  
Author(s):  
Martina Rimmele ◽  
Wojciech Nogala ◽  
Maryam Seif-Eddine ◽  
Maxie M. Roessler ◽  
Martin Heeney ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Structural Changes ◽  
Molecular Design ◽  
Experimental Studies ◽  
Design Guidelines ◽  
Structure Property ◽  
Structural Variations ◽  
Ring Currents ◽  
Conjugated Macrocycles

π-Conjugated macrocycles are molecules with unique properties that are increasingly exploited for applications and the question of whether they can sustain global aromatic or antiaromatic ring currents is particularly intriguing. However, there are only a small number of experimental studies that investigate how the properties of π-conjugated macrocycles evolve with systematic structural changes. Here, we present such a systematic experimental study of a set of [2.2.2.2]cyclophanetetraenes, all with formally Hückel antiaromatic ground states, and combine it with an in-depth computational analysis. The study reveals the central role of local and global aromaticity for rationalizing the observed optoelectronic properties, ranging from extremely large Stokes shifts of up to 1.6 eV to reversible fourfold reduction, a highly useful feature for charge storage/accumulation applications. A recently developed method for the visualization of chemical shielding tensors (VIST) is applied to provide unique insight into local and global ring currents occurring in different planes along the macrocycle. Conformational changes as a result of the structural variations can further explain some of the observations. The study contributes to the development of structure–property relationships and molecular design guidelines and will help to understand, rationalize, and predict the properties of other π-conjugated macrocycles.

scholarly journals Functional Group Introduction and Aromatic Unit Variation in a Set of π-Conjugated Macrocycles: Revealing the Central Role of Local and Global Aromaticity

2021 ◽  
Author(s):  
Martina Rimmele ◽  
Wojciech Nogala ◽  
Maryam Seif-Eddine ◽  
Maxie M. Roessler ◽  
Martin Heeney ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Structural Changes ◽  
Molecular Design ◽  
Experimental Studies ◽  
Design Guidelines ◽  
Structure Property ◽  
Structural Variations ◽  
Ring Currents ◽  
Conjugated Macrocycles

π-Conjugated macrocycles are molecules with unique properties that are increasingly exploited for applications and the question of whether they can sustain global aromatic or antiaromatic ring currents is particularly intriguing. However, there are only a small number of experimental studies that investigate how the properties of π-conjugated macrocycles evolve with systematic structural changes. Here, we present such a systematic experimental study of a set of [2.2.2.2]cyclophanetetraenes, all with formally Hückel antiaromatic ground states, and combine it with an in-depth computational analysis. The study reveals the central role of local and global aromaticity for rationalizing the observed optoelectronic properties, ranging from extremely large Stokes shifts of up to 1.6 eV to reversible fourfold reduction, a highly useful feature for charge storage/accumulation applications. A recently developed method for the visualization of chemical shielding tensors (VIST) is applied to provide unique insight into local and global ring currents occurring in different planes along the macrocycle. Conformational changes as a result of the structural variations can further explain some of the observations. The study contributes to the development of structure–property relationships and molecular design guidelines and will help to understand, rationalize, and predict the properties of other π-conjugated macrocycles.

scholarly journals Functional group introduction and aromatic unit variation in a set of π‑conjugated macrocycles: revealing the central role of local and global aromaticity

2021 ◽  
Author(s):  
Martina Rimmele ◽  
Wojciech Nogala ◽  
Maryam Seif-Eddine ◽  
Maxie Roessler ◽  
Martin Heeney ◽  
...  
Keyword(s):  
Functional Group ◽  
Ring Currents ◽  
Conjugated Macrocycles

π-Conjugated macrocycles are molecules with unique properties that are increasingly exploited for applications and the question of whether they can sustain global aromatic or antiaromatic ring currents is particularly intriguing....

scholarly journals Surface-Exposed Adeno-Associated Virus Vp1-NLS Capsid Fusion Protein Rescues Infectivity of Noninfectious Wild-Type Vp2/Vp3 and Vp3-Only Capsids but Not That of Fivefold Pore Mutant Virions

2007 ◽  
Vol 81 (15) ◽  
pp. 7833-7843 ◽  
Author(s):  
Joshua C. Grieger ◽  
Jarrod S. Johnson ◽  
Brittney Gurda-Whitaker ◽  
Mavis Agbandje-McKenna ◽  
R. Jude Samulski
Keyword(s):  
Conformational Changes ◽  
Structural Changes ◽  
Wild Type ◽  
Dot Blot ◽  
Adeno Associated Virus ◽  
N Terminus ◽  
Localization Signal ◽  
Significant Effort

ABSTRACT Over the past 2 decades, significant effort has been dedicated to the development of adeno-associated virus (AAV) as a vector for human gene therapy. However, understanding of the virus with respect to the functional domains of the capsid remains incomplete. In this study, the goal was to further examine the role of the unique Vp1 N terminus, the N terminus plus the recently identified nuclear localization signal (NLS) (J. C. Grieger, S. Snowdy, and R. J. Samulski, J. Virol 80:5199-5210, 2006), and the virion pore at the fivefold axis in infection. We generated two Vp1 fusion proteins (Vp1 and Vp1NLS) linked to the 8-kDa chemokine domain of rat fractalkine (FKN) for the purpose of surface exposure upon assembly of the virion, as previously described (K. H. Warrington, Jr., O. S. Gorbatyuk, J. K. Harrison, S. R. Opie, S. Zolotukhin, and N. Muzyczka, J. Virol 78:6595-6609, 2004). The unique Vp1 N termini were found to be exposed on the surfaces of these capsids and maintained their phospholipase A2 (PLA2) activity, as determined by native dot blot Western and PLA2 assays, respectively. Incorporation of the fusions into AAV type 2 capsids lacking a wild-type Vp1, i.e., Vp2/Vp3 and Vp3 capsid only, increased infectivity by 3- to 5-fold (Vp1FKN) and 10- to 100-fold (Vp1NLSFKN), respectively. However, the surface-exposed fusions did not restore infectivity to AAV virions containing mutations at a conserved leucine (Leu336Ala, Leu336Cys, or Leu336Trp) located at the base of the fivefold pore. EM analyses suggest that Leu336 may play a role in global structural changes to the virion directly impacting downstream conformational changes essential for infectivity and not only have local effects within the pore, as previously suggested.

scholarly journals On the (un)coupling of the chromophore, tongue interactions, and overall conformation in a bacterial phytochrome

2018 ◽  
Vol 293 (21) ◽  
pp. 8161-8172 ◽  
Author(s):  
Heikki Takala ◽  
Heli K. Lehtivuori ◽  
Oskar Berntsson ◽  
Ashley Hughes ◽  
Rahul Nanekar ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Structural Changes ◽  
Deinococcus Radiodurans ◽  
Red Light ◽  
Light Responses ◽  
Structural Mechanism ◽  
Weakly Coupled ◽  
Activity State ◽  
Conserved Tyrosine

Phytochromes are photoreceptors in plants, fungi, and various microorganisms and cycle between metastable red light–absorbing (Pr) and far-red light–absorbing (Pfr) states. Their light responses are thought to follow a conserved structural mechanism that is triggered by isomerization of the chromophore. Downstream structural changes involve refolding of the so-called tongue extension of the phytochrome-specific GAF-related (PHY) domain of the photoreceptor. The tongue is connected to the chromophore by conserved DIP and PRXSF motifs and a conserved tyrosine, but the role of these residues in signal transduction is not clear. Here, we examine the tongue interactions and their interplay with the chromophore by substituting the conserved tyrosine (Tyr263) in the phytochrome from the extremophile bacterium Deinococcus radiodurans with phenylalanine. Using optical and FTIR spectroscopy, X-ray solution scattering, and crystallography of chromophore-binding domain (CBD) and CBD–PHY fragments, we show that the absence of the Tyr263 hydroxyl destabilizes the β-sheet conformation of the tongue. This allowed the phytochrome to adopt an α-helical tongue conformation regardless of the chromophore state, hence distorting the activity state of the protein. Our crystal structures further revealed that water interactions are missing in the Y263F mutant, correlating with a decrease of the photoconversion yield and underpinning the functional role of Tyr263 in phytochrome conformational changes. We propose a model in which isomerization of the chromophore, refolding of the tongue, and globular conformational changes are represented as weakly coupled equilibria. The results also suggest that the phytochromes have several redundant signaling routes.

A sample cell forin situelectric-field-dependent structural characterization and macroscopic strain measurements

2016 ◽  
Vol 23 (3) ◽  
pp. 694-699 ◽  
Author(s):  
Mohammad J. Hossain ◽  
Lijun Wang ◽  
Zhiyang Wang ◽  
Neamul H. Khansur ◽  
Manuel Hinterstein ◽  
...  
Keyword(s):  
Structural Changes ◽  
Linear Displacement ◽  
Displacement Sensor ◽  
Macroscopic Strain ◽  
Structure Property ◽  
X Ray Diffraction ◽  
Sample Cell ◽  
Structural Variations ◽  
X Ray ◽  
Electric Potentials

When studying electro-mechanical materials, observing the structural changes during the actuation process is necessary for gaining a complete picture of the structure–property relationship as certain mechanisms may be meta-stable during actuation.In situdiffraction methods offer a powerful and direct means of quantifying the structural contributions to the macroscopic strain of these materials. Here, a sample cell is demonstrated capable of measuring the structural variations of electro-mechanical materials under applied electric potentials up to 10 kV. The cell is designed for use with X-ray scattering techniques in reflection geometry, while simultaneously collecting macroscopic strain data using a linear displacement sensor. The results show that the macroscopic strain measured using the cell can be directly correlated with the microscopic response of the material obtained from diffraction data. The capabilities of the cell have been successfully demonstrated at the Powder Diffraction beamline of the Australian Synchrotron and the potential implementation of this cell with laboratory X-ray diffraction instrumentation is also discussed.

scholarly journals Aminoglycoside ribosome interactions reveal novel conformational states at ambient temperature

2018 ◽  
Author(s):  
Mary E. O’Sullivan ◽  
Frédéric Poitevin ◽  
Raymond G. Sierra ◽  
Cornelius Gati ◽  
E. Han Dao ◽  
...  
Keyword(s):  
Ambient Temperature ◽  
Binding Site ◽  
Conformational Changes ◽  
Structural Changes ◽  
Ribosomal Subunit ◽  
Drug Binding ◽  
Biologically Relevant ◽  
Drug Binding Site ◽  
Local Antibiotic

ABSTRACTThe bacterial 30S ribosomal subunit is a primary antibiotic target. Despite decades of discovery, the mechanisms by which antibiotic binding induces ribosomal dysfunction are not fully understood. Ambient temperature crystallographic techniques allow more biologically relevant investigation of how local antibiotic binding site interactions trigger global subunit rearrangements that perturb protein synthesis. Here, the structural effects of 2-deoxystreptamine (paromomycin and sisomicin), a novel sisomicin derivative, N1-methyl sulfonyl sisomicin (N1MS) and the non-deoxystreptamine (streptomycin) aminoglycosides on the ribosome at ambient and cryogenic temperatures were examined. Comparative studies led to three main observations. First, individual aminoglycoside-ribosome interactions in the decoding center were similar for cryogenic vs ambient temperature structures. Second, analysis of a highly conserved GGAA tetraloop of h45 revealed aminoglycoside-specific conformational changes, which are affected by temperature only for N1MS. We report the h44/h45 interface in varying states, that is, engaged, disengaged and in equilibrium. Thirdly, we observe aminoglycoside-induced effects on 30S domain closure, including a novel intermediary closure state, which is also sensitive to temperature. Analysis of three ambient and five cryogenic crystallography datasets reveal a correlation between h44/h45 engagement and domain closure. These observations illustrate the role of ambient temperature crystallography in identifying dynamic mechanisms of ribosomal dysfunction induced by local drug-binding site interactions. Together these data identify tertiary ribosomal structural changes induced by aminoglycoside binding that provides functional insight and targets for drug design.

scholarly journals Identification of Chromosomes and Chromosome Rearrangements in Crop Brassicas and Raphanus sativus: A Cytogenetic Toolkit Using Synthesized Massive Oligonucleotide Libraries

2020 ◽  
Vol 11 ◽  
Author(s):  
Neha Agrawal ◽  
Mehak Gupta ◽  
Surinder S. Banga ◽  
JS (Pat) Heslop-Harrison
Keyword(s):  
Structural Changes ◽  
Chromosomal Mapping ◽  
Structural Variations ◽  
Breeding Programs ◽  
Pak Choi ◽  
Bioinformatic Pipeline ◽  
A Genome ◽  
The Family

Crop brassicas include three diploid [Brassica rapa (AA; 2n = 2x = 16), B. nigra (BB; 2n = 2x = 18), and B. oleracea (CC; 2n = 2x = 20)] and three derived allotetraploid species. It is difficult to distinguish Brassica chromosomes as they are small and morphologically similar. We aimed to develop a genome-sequence based cytogenetic toolkit for reproducible identification of Brassica chromosomes and their structural variations. A bioinformatic pipeline was used to extract repeat-free sequences from the whole genome assembly of B. rapa. Identified sequences were subsequently used to develop four c. 47-mer oligonucleotide libraries comprising 27,100, 11,084, 9,291, and 16,312 oligonucleotides. We selected these oligonucleotides after removing repeats from 18 identified sites (500–1,000 kb) with 1,997–5,420 oligonucleotides localized at each site in B. rapa. For one set of probes, a new method for amplification or immortalization of the library is described. oligonucleotide probes produced specific and reproducible in situ hybridization patterns for all chromosomes belonging to A, B, C, and R (Raphanus sativus) genomes. The probes were able to identify structural changes between the genomes, including translocations, fusions, and deletions. Furthermore, the probes were able to identify a structural translocation between a pak choi and turnip cultivar of B. rapa. Overall, the comparative chromosomal mapping helps understand the role of chromosome structural changes during genome evolution and speciation in the family Brassicaceae. The probes can also be used to identify chromosomes in aneuploids such as addition lines used for gene mapping, and to track transfer of chromosomes in hybridization and breeding programs.

scholarly journals Molecular Dynamics of SARS-CoV-2 Nsp1 Structural Changes Associated with Variant Mutations

2021 ◽  
Author(s):  
Shokouh Rezaei ◽  
Yahya Sefidbakht ◽  
Filipe Pereira
Keyword(s):  
Molecular Dynamics ◽  
Conformational Changes ◽  
Structural Changes ◽  
Structure And Function ◽  
Dynamics Simulation ◽  
Structural Protein ◽  
Wild Type ◽  
Deletion Mutations ◽  
And Function

Abstract SARS-CoV-2 non-structural protein 1 (Nsp1) is a virulence factor that inhibits the translation of host mRNAs and interact with viral RNA. Despite the relevance of Nsp1, few studies have been conducted to understand the effect of mutations on Nsp1 structure and function. Here, we provide a molecular dynamics simulation of SARS-CoV-2 Nsp1, wild type and variants. We found that SARS-CoV-2 Nsp1 has a more Rg value than SARS-CoV-1 Nsp1, with indicate an effect on the folding protein. This result suggest that SARS-CoV-2 Nsp1 can more easily approach the active site of the ribosome compared to SARS-CoV-1 Nsp1. In addition, we found that the C-terminal of the SARS-CoV-2 Nsp1, in particular residues 164 to 170, are more flexible than other regions of SARS-CoV-2 Nsp1 and SARS-CoV-1 Nsp1, confirming the role of this region in the interaction with the 40S subunit. Moreover, multiple deletion mutations have been found in the N/C-terminal of the SARS-CoV-2 Nsp1, which seems the effect of SARS-CoV-2 Nsp1 multiple deletions is greater than that of substitutions. Among all deletions, D156-158 and D80-90 may destabilize the protein structure and possibly increase the virulence of the SARS-CoV-2. Overall, our findings reinforce the importance of studying Nsp1 conformational changes in new variants and its effect on virulence of SARS-CoV-2.

scholarly journals The role of ATP in the function of human ORC4 protein

2010 ◽  
Vol 75 (3) ◽  
pp. 317-322
Author(s):  
Aleksandra Divac ◽  
Branko Tomic ◽  
Jelena Kusic
Keyword(s):  
Conformational Changes ◽  
Origin Recognition Complex ◽  
Structural Changes ◽  
Atp Hydrolysis ◽  
Protein A ◽  
Structural Role ◽  
A Subunit ◽  
Dna Substrates ◽  
Origin Recognition

Human ORC4 protein, a subunit of the origin recognition complex, belongs to the AAA+ superfamily of ATPases. Proteins belonging to this family require ATP for their function and interactions with ATP lead to conformational changes in them or in their partners. Human ORC4 protein induces structural changes in DNA substrates, promoting renaturation and formation of non-canonical structures, as well as conversion of single-stranded into multi-stranded oligonucleotide structures. The aim of this study was to further investigate the role of ATP in the function of human ORC4 protein. For this purpose, a mutant in the conserved Walker B motif of ORC4, which is able to bind but not to hydrolyze ATP, was constructed and its activity in DNA restructuring reactions was investigated. The obtained results showed that ATP hydrolysis is not necessary for the function of human ORC4. It is proposed that ATP has a structural role as a cofactor in the function of human ORC4 as a DNA restructuring agent.

scholarly journals Targeting C-Reactive Protein in Inflammatory Disease by Preventing Conformational Changes

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
J. R. Thiele ◽  
J. Zeller ◽  
H. Bannasch ◽  
G. B. Stark ◽  
K. Peter ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Structural Changes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
C Reactive Protein ◽  
Inflammatory Reactions ◽  
Reactive Protein ◽  
Dissociation Mechanism ◽  
Proinflammatory Mediators

C-reactive protein (CRP) is a pentraxin that has long been employed as a marker of inflammation in clinical practice. Recent findings brought up the idea of CRP to be not only a systemic marker but also a mediator of inflammation. New studies focused on structural changes of the plasma protein, revealing the existence of two distinct protein conformations associated with opposed inflammatory properties. Native, pentameric CRP (pCRP) is considered to be the circulating precursor form of monomeric CRP (mCRP) that has been identified to be strongly proinflammatory. Recently, a dissociation mechanism of pCRP has been identified on activated platelets and activated/apoptotic cells associated with the amplification of the proinflammatory potential. Correspondingly, CRP deposits found in inflamed tissues have been identified to exhibit the monomeric conformation by using conformation-specific antibodies. Here we review the current literature on the causal role of the dissociation mechanism of pCRP and the genesis of mCRP for the amplification of the proinflammatory potential in inflammatory reactions such as atherosclerosis and ischemia/reperfusion injury. The chance to prevent the formation of proinflammatory mediators in ubiquitous inflammatory cascades has pushed therapeutic strategies by targeting pCRP dissociation in inflammation. In this respect, the development of clinically applicable derivatives of the palindromic compound 1,6-bis(phosphocholine)-hexane (1,6-bis PC) should be a major focus of future CRP research.

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