Author Archive

EGFR activation dynamics, inhibiting MRSA and transcription factor diffusion

Don’t know what to do with your Friday afternoon? Why not take a look at our latest HOT article! We make all our HOT articles free to access for 4 weeks:

Integrated experimental and model-based analysis reveals the spatial aspects of EGFR activation dynamics
Harish Shankaran,  Yi Zhang,  William B. Chrisler,  Jonathan A. Ewald,  H. Steven Wiley and Haluk Resat
DOI: 10.1039/C2MB25190F

Or if that’s not in your field, we’ve also just published two new review articles:

Computational models for large-scale simulations of facilitated diffusion
Nicolae Radu Zabet and Boris Adryan
DOI: 10.1039/C2MB25201E

Inhibitors targeting on cell wall biosynthesis pathway of MRSA
Haihong Hao,  Guyue Cheng,  Menghong Dai,  Qinghua Wu and Zonghui Yuan
DOI: 10.1039/C2MB25188D

Access to free content is provided to individuals through a free RSC Personal Publishing Account.

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Emerging Investigators 2012

Molecular BioSystems Emerging Investigators 2012We are delighted to publish our third themed issue dedicated to the work of new and emerging investigators whose research in chemical biology interfaces with the -omic sciences and systems biology.

There is plenty of exciting research in this issue, including work from Priscilla Yang on exploiting known kinase inhibitors to develop new probes for imaging kinases and Nuno Bandeira on spectral networks algorithms to analyse tandem mass spectroscopy results. Both these articles are free to access for the next four weeks.

For all the contributors to the issue please see our Profile article.

To coincide with this, Molecular BioSystems Deputy Editor Victoria Eyley has just returned from the International Conference on Systems Biology (ICSB) in Toronto, Canada where she presented this year’s Early Career Lectureship to Thijn Brummelkamp (The Netherlands Cancer Institute). Thijn is being recognised as he was one of the first to describe stable RNA interference, which is widely used to study gene function.

*Free access is provided to subscribing institutions or through an RSC Publishing Personal Account. Registration is quick and easy at http://pubs.rsc.org/en/account/register.

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Reviewing techniques to understand the role of oxidative stress in psychiatric disorders

In this review Ana Cristina Andreazza looks at the use of redox-proteomics and epigenomics to improve our understanding of the pathophysiology of psychiatric illnesses such as biopolar disorder and schizophrenia.  Oxidative stress and mitochondrial dysfunction have recently been implicated as common features in major psychiatric disorders, but only through a combination of techniques can we begin to understand the nature of oxidative modification, its potential to change protein–protein interactions and induce epigenetic modification says Andreazza.  Understanding the molecular targets for oxidation should hopefully lead to the development of new drug treatments or disease biomarkers.

The review covers:
1. Oxidative stress and redox balance
2. The link between DNA oxidation and DNA methylation
3. Psychiatry and oxidative stress: what do we know so far?
4. Developing biomarkers to assist in predicting the course of psychiatric illnesses

Combining redox-proteomics and epigenomics to explain the involvement of oxidative stress in psychiatric disorders
Ana Cristina Andreazza
DOI: 10.1039/C2MB25118C

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Wheat lectin shows potential as targeted carrier for anticancer drugs

A lectin from wheat, wheat germ agglutinin (WGA),  has the potential to help target anticancer agents to tumour cells Vanya Bogoeva and colleagues from the Bulgarian Academy of Sciences and Sophia University have found.

One of the issues with current anticancer drugs, such as cis-platin, is that they are non-specific to tumour tissue, and so can cause severe side effects by destroying normal cells. WGA can recognise cancer cells, and is taken up by them – it also has a high affinity for four metal-based anticancer agents: cisplatin, a Pt porphyrin and two gold porphyrins and therefore may have potential as a drug delivery molecule for metal-based anticancer drugs.

As with all our HOT articles, this one is free to access for 4 weeks following a simple registration:

Characterization of metalloanticancer capacity of an agglutinin from wheat
Vanya P. Bogoeva,  Lidiya P. Petrova,  Ivan B. Ivanov,  Hristina N. Kulina and Ivan Ch. Buchvarov
DOI: 10.1039/C2MB25186H

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Binding of phenolic hydrazones to macrophage migration inhibitory factor modelled

In this HOT article Tingjun Hou and colleagues from Soochow University have studied the interactions between macrophage migration inhibitory factor (MIF) with a series of phenolic hydrazones via a series of computational approaches.  MIF is implicated in a number of inflammatory diseases such as arthritis, asthma,  and more recently has been shown to have a role in the formation of tumors.  Phenolic hydrazones have been demonstrated to inhibit MIF, but the binding was not understood until now.  Hou et al describe a set of interactions that may be used to further develop the phenolic hydrazone scaffold for MIF inhibition and describe three derivatives that show ‘promising potency’.

Understanding microscopic binding of macrophage migration inhibitory factor with phenolic hydrazones by molecular docking, molecular dynamics simulations and free energy calculationsUnderstanding microscopic binding of macrophage migration inhibitory factor with phenolic hydrazones by molecular docking, molecular dynamics simulations and free energy calculations
Lei Xu,  Youyong Li,  Lin Li,  Shunye Zhou and Tingjun Hou
DOI: 10.1039/C2MB25146A

As with all our HOT articles this one is free to access for the next four weeks (following a simple registration for an RSC Publishing account)

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Transforming the hydroxyl group

The hydroxyl group is a tricky moiety to convert to another functional group, as it is less reactive than other common groups such as amines, thiols or carboxylic acids and reactions are often thwarted by the presence of water.  It is, however, present in many biologically significant molecules – ~65% of known natural products, ~40% of drugs, several classes of lipids and three of the 20 common amino acids according to this review by Darci J. Trader and Erin E. Carlson.   They look at the currently available methods to transform this important group, with particular emphasis on methods that are useful for chemical biology applications.

Areas covered include:

  • Direct conjugation reactions
  • Activation by generation of a leaving groupHydroxyl group transformations for chemical biology
  • Alcohol oxidation
  • Transformation to an alternative chemical handle
  • Natural product analog for target identification
  • Functional group-mediated enrichment of alcohols
  • Chemoselective protein bioconjugation
  • Hydroxyl groups in enzyme active sites

Chemoselective hydroxyl group transformation: an elusive target
Darci J. Trader and Erin E. Carlson
DOI: 10.1039/C2MB25122A

This paper is free to access for 4 weeks following a simple registration for individual users.

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Proteome analysis reveals pretubulysin is selective for beta-tubulin

Pretubulysin derived probes as novel tools for monitoring the microtubule network via activity-based protein profiling and fluorescence microscopy This HOT paper from Stephen Sieber (University of Munich) and colleagues have performed a whole proteome analysis to demonstrate for the first time that pretubulysin is selective for beta-tubulin.  Pretubulysins are simpler analogues of the natural products tubulysins, which are extremely effective at inhibiting formation of microtubules.  Microtubules  play a major role in mitosis and are thus a therapeutic target for conditions such as cancer.

Sieber et al have derived two photoaffinity probes from pretublysin and showed that pretublysin, like tubulysin, specifically binds to tubulin and therefore could potentially be a simpler molecule for future drug development.

Pretubulysin derived probes as novel tools for monitoring the microtubule network via activity-based protein profiling and fluorescence microscopy
Jürgen Eirich,  Jens L. Burkhart,  Angelika Ullrich,  Georg C. Rudolf,  Angelika Vollmar,  Stefan Zahler,  Uli Kazmaier and Stephan A. Sieber
DOI: 10.1039/C2MB25144B

This paper is free to access for 4 weeks following a simple registration for individual users.

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Easy Abl expression and the origins of ubiquitination on the cover of Issue 7

On the front covers of this month’s issue are from two HOT articles from Koby Levy and David Cowburn.

The article from Koby Levy and colleagues at Weizmann Institute of Science, Israel, addresses the origins of protein ubiquitination, a major regulatory mechanism involved in many important cellular pathways.  They quantify the rates of evolutionary changes of ubiquitination and small ubiquitin-like modifier) sites, estimating when they first appeared and compare them to acetylation and phosphorylation sites and unmodified residues.

The origins and evolution of ubiquitination sites
Tzachi Hagai, Ágnes Tóth-Petróczy, Ariel Azia and Yaakov Levy
DOI: 10.1039/C2MB25052G

David Cowburn’s team from the Albert Einstein College of Medicine of Yeshiva University, USA, have devised a simple method to express and purify isolated Abl kinase domain and SH3–SH2–kinase multi-domain structures.  Due to the involvement of tyrosine kinases in cell development, and the associated implications for development and cancer resulting from changes in kinase structures, tyrosine kinases are being targeted for molecular therapeutics.  However, expressing tyrosine kinases as recombinant forms in bacterial systems for study has to date been a challenge. Cowburn et al’s method provides new avenues for structure–function studies, as the expressed Abl proteins retain correct folding and biological function, and segments can be isotopically labelled.

Abl kinase constructs expressed in bacteria: facilitation of structural and functional studies including segmental labeling by expressed protein ligation
Rong Xu, Dongsheng Liu and David Cowburn
DOI: 10.1039/C2MB25051A

As with all our cover articles, both of these are free to access (following a simple registration) for 6 weeks.

View the rest of Issue 7 here

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A systems-level review of lipid synthesis in plant cells

The synthesis of membrane lipids in chloroplasts is part of an enormously complex larger system in plant cells, and in this article Eric Maréchal and colleagues review our understanding of galactolipid homeostasis in terms of the complete system.  They discuss approaches that may resolve unanswered questions such as the relationship between lipid metabolism and plant development, and propose galvestine-1 as a potential tool for future studies.

Galvestine-1, a novel chemical probe for the study of the glycerolipid homeostasis system in plant cells
Laurence Boudière,  Cyrille Y. Botté,  Nadia Saidani,  Mathieu Lajoie,  Jessica Marion,  Laurent Bréhélin,  Yoshiki Yamaryo-Botté,  Béatrice Satiat-Jeunemaître,  Christelle Breton,  Agnès Girard-Egrot,  Olivier Bastien,  Juliette Jouhet,  Denis Falconet,  Maryse A. Block and Eric Maréchal
DOI: 10.1039/C2MB25067E

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Sequencing proteoglycans and bacterical genomics on the cover of Issue 6

On the cover of this month’s issue we have two interesting review articles from Robert J. Linhardt et al. and Alla Gagarinova et al.

Proteoglycan sequenceRobert J. Linhardt and colleagues discuss the difficulties in sequencing complex proteoglycans, and the advances made in the field during the last decade.

Proteoglycan sequence
Lingyun Li, Mellisa Ly and Robert J. Linhardt
DOI: 10.1039/C2MB25021G

Genome-scale genetic manipulation methods for exploring bacterial molecular biologyMeanwhile, Alla Gagarinova and Andrew Emili discuss the recent introduction of large-scale genetic manipulation and screening procedures which are progressing our understanding of bacterial genetics:

Genome-scale genetic manipulation methods for exploring bacterial molecular biology
Alla Gagarinova and Andrew Emili
DOI: 10.1039/C2MB25040C

Also in this issue is an Opinion article from Bernard M. Corfe, in which he proposes a hypothesis to unify the integration of the metabolic and HDAC inhibitory properties of short-chain fatty acids.

Hypothesis: butyrate is not an HDAC inhibitor, but a product inhibitor of deacetylation

View the whole issue here

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