scholarly journals The Impact of Retinal Configuration on the Protein-Chromophore Interactions in Bistable Jumping Spider Rhodopsin-1

2021 ◽  
Author(s):  
Jonathan Richard Church ◽  
Jógvan Magnus Haugaard Olsen ◽  
Igor Schapiro
Keyword(s):  
Absorption Maximum ◽  
Specific Interactions ◽  
Hydrogen Bond Network ◽  
Jumping Spider ◽  
Broad Application ◽  
Ability To Act ◽  
Bond Network ◽  
Stable Forms ◽  
The Impact ◽  
Insight Into

Bistable rhodopsins have two stable forms which can be interconverted by light. Due to their ability to act as photoswitches, these proteins are considered as ideal candidates for applica-tions such as optogenetics. In this work we analyze a recently crystalized bistable rhodopsin, namely the jumping spider rhodopsin-1 (JSR1). This rhodopsin exhibits identical absorption maxima for the parent and the photoproduct form, which impedes its broad application. We have performed hybrid QM/MM simulations to study three isomers of the retinal chromo-phore: the 9-cis, 11-cis and all-trans configurations. The main aim was to gain insight into the specific interactions of each isomer and their impact on the absorption maximum in JSR1. The absorption spectra were computed using sampled snapshots from a QM/MM molecular dy-namics trajectory and compared to experimental counterparts. The chromophore-protein in-teractions were analyzed by visualizing the electrostatic potential of the protein and projecting it onto chromophore. It was found that the distance between a nearby tyrosine (Y126) residue plays a larger role in the predicted absorption maximum than the primary counterion (E194). Geometric differences between the isomers were also noted including a structural change in the polyene chain of the chromophore as well as changes in the nearby hydrogen bond network.

scholarly journals The Impact of Retinal Configuration on the Protein–Chromophore Interactions in Bistable Jumping Spider Rhodopsin-1

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 71
Author(s):  
Jonathan R. Church ◽  
Jógvan Magnus Haugaard Olsen ◽  
Igor Schapiro
Keyword(s):  
Protein Interactions ◽  
Absorption Maximum ◽  
Specific Interactions ◽  
Jumping Spider ◽  
Broad Application ◽  
Ability To Act ◽  
Retinal Chromophore ◽  
Stable Forms ◽  
The Impact ◽  
Insight Into

Bistable rhodopsins have two stable forms that can be interconverted by light. Due to their ability to act as photoswitches, these proteins are considered as ideal candidates for applications such as optogenetics. In this work, we analyze a recently crystalized bistable rhodopsin, namely the jumping spider rhodopsin-1 (JSR1). This rhodopsin exhibits identical absorption maxima for the parent and the photoproduct form, which impedes its broad application. We performed hybrid QM/MM simulations to study three isomers of the retinal chromophore: the 9-cis, 11-cis and all-trans configurations. The main aim was to gain insight into the specific interactions of each isomer and their impact on the absorption maximum in JSR1. The absorption spectra were computed using sampled snapshots from QM/MM molecular dynamics trajectories and compared to their experimental counterparts. The chromophore–protein interactions were analyzed by visualizing the electrostatic potential of the protein and projecting it onto the chromophore. It was found that the distance between a nearby tyrosine (Y126) residue plays a larger role in the predicted absorption maximum than the primary counterion (E194). Geometric differences between the isomers were also noted, including a structural change in the polyene chain of the chromophore, as well as changes in the nearby hydrogen bonding network.

scholarly journals Rational engineering of L-asparaginase reveals importance of dual activity for cancer cell toxicity

Blood ◽  
2011 ◽  
Vol 117 (5) ◽  
pp. 1614-1621 ◽  
Author(s):  
Marc N. Offman ◽  
Marcin Krol ◽  
Naina Patel ◽  
Shekhar Krishnan ◽  
JiZhong Liu ◽  
...  
Keyword(s):  
Cysteine Proteases ◽  
Hydrogen Bond Network ◽  
Cell Toxicity ◽  
Rational Engineering ◽  
Therapeutic Context ◽  
Bond Network ◽  
The Impact ◽  
Glutaminase Activity ◽  
Protein Macromolecule ◽  
Tetrameric Form

Abstract Using proteins in a therapeutic context often requires engineering to modify functionality and enhance efficacy. We have previously reported that the therapeutic antileukemic protein macromolecule Escherichia coli L-asparaginase is degraded by leukemic lysosomal cysteine proteases. In the present study, we successfully engineered L-asparaginaseto resist proteolytic cleavage and at the same time improve activity. We employed a novel combination of mutant sampling using a genetic algorithm in tandem with flexibility studies using molecular dynamics to investigate the impact of lid-loop and mutations on drug activity. Applying these methods, we successfully predicted the more active L-asparaginase mutants N24T and N24A. For the latter, a unique hydrogen bond network contributes to higher activity. Furthermore, interface mutations controlling secondary glutaminase activity demonstrated the importance of this enzymatic activity for drug cytotoxicity. All selected mutants were expressed, purified, and tested for activity and for their ability to form the active tetrameric form. By introducing the N24A and N24A R195S mutations to the drug L-asparaginase, we are a step closer to individualized drug design.

X-ray Crystallographic Study of Alkylammonium Anthracene-9-carboxylates as a Model for Fibrous Structure of Binary Anthracene Salt Gels

2004 ◽  
Vol 69 (6) ◽  
pp. 1292-1300 ◽  
Author(s):  
Tahahiro Tani ◽  
Kazuki Sada ◽  
Masatsugu Ayabe ◽  
Yuya Iwashita ◽  
Takanori Kishida ◽  
...  
Keyword(s):  
Alkyl Chain ◽  
Columnar Structure ◽  
Hydrogen Bond Network ◽  
One Dimensional ◽  
X Ray ◽  
Crystallographic Study ◽  
Alkylammonium Salts ◽  
Bond Network ◽  
Fibrous Assemblies ◽  
Long Alkyl Chain

Crystal structure of hexylammonium anthracene-9-carboxylate was investigated. The salt was arranged by a one-dimensional hydrogen bond network to form a columnar structure in the crystalline state. This columnar structure should be the model of fibrous assemblies in the organogels of anthracene-9-carboxylate alkylammonium salts having a long alkyl chain.

Halides of Macrocyclic Silver(II) Complexes: Crystal Structures with Hydrogen Bond Network and Reaction Kinetics of the Decomposition

2021 ◽  
pp. 120431
Author(s):  
Akinori Honda ◽  
Shunta Kakihara ◽  
Shuhei Ichimura ◽  
Kazuaki Tomono ◽  
Mina Matsushita ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Reaction Kinetics ◽  
Crystal Structures ◽  
Hydrogen Bond Network ◽  
Bond Network ◽  
Kinetics Of

scholarly journals Changing landscapes: Gay men in the west and northwest of Ireland

Sexualities ◽  
2020 ◽  
pp. 136346072098169
Author(s):  
Aidan McKearney
Keyword(s):  
Gay Men ◽  
Social Rights ◽  
Irish Society ◽  
Recent Past ◽  
Same Sex ◽  
Lgbt People ◽  
The Many ◽  
Northwest Region ◽  
The Impact ◽  
Insight Into

This article focuses on the experiences of gay men in the rural west and northwest region of Ireland, during a period of transformational social and political change in Irish society. These changes have helped facilitate new forms of LGBTQI visibility, and local radicalism in the region. Same-sex weddings, establishment of rural LGBT groups and marching under an LGBT banner at St Patricks Day parades would have been unthinkable in the recent past; but they are now becoming a reality. The men report continuing challenges in their lives as gay men in the nonmetropolitan space, but the emergence of new visibility, voice and cultural acceptance of LGBT people is helping change their lived experiences. The study demonstrates the impact of local activist LGBT citizens. Through their testimonies we can gain an insight into the many, varied and interwoven factors that have interplayed to create the conditions necessary for the men to: increasingly define themselves as gay to greater numbers of people in their localities; to embrace greater visibility and eschew strategies of silence; and aspire to a host of legal, political, cultural and social rights including same-sex marriage. Organic forms of visibility and local radicalism have emerged in the region and through an analysis of their testimonies we can see how the men continue to be transformed by an ever-changing landscape.

Double, triple or quadruple hits? Exploring the impact of cybercrime on victims in the Netherlands

2021 ◽  
pp. 026975802110106
Author(s):  
Raoul Notté ◽  
E.R. Leukfeldt ◽  
Marijke Malsch
Keyword(s):  
Public Opinion ◽  
Literature Review ◽  
The Netherlands ◽  
Public Discourse ◽  
Moral Judgments ◽  
Victim Blaming ◽  
High Prevalence ◽  
Different Types ◽  
The Impact ◽  
Insight Into

This article explores the impact of online crime victimisation. A literature review and 41 interviews – 19 with victims and 22 with experts – were carried out to gain insight into this. The interviews show that most impacts of online offences correspond to the impacts of traditional offline offences. There are also differences with offline crime victimisation. Several forms of impact seem to be specific to victims of online crime: the substantial scale and visibility of victimhood, victimisation that does not stop in time, the interwovenness of online and offline, and victim blaming. Victims suffer from double, triple or even quadruple hits; it is the accumulation of different types of impact, enforced by the limitlessness in time and space, which makes online crime victimisation so extremely invasive. Furthermore, the characteristics of online crime victimisation greatly complicate the fight against and prevention of online crime. Finally, the high prevalence of cybercrime victimisation combined with the severe impact of these crimes seems contradictory with public opinion – and associated moral judgments – on victims. Further research into the dominant public discourse on victimisation and how this affects the functioning of the police and victim support would be valuable.

Sign in / Sign up

Export Citation Format

Share Document