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Efflux is one of the mechanisms employed by Gram-negative bacteria to become resistant to routinely used antibiotics. The inhibition of efflux by targeting their regulators is a promising strategy to re-sensitize bacterial pathogens to antibiotics. AcrAB-TolC is the main resistance-nodulation-division efflux pump in Enterobacteriaceae. MarA is an AraC/XylS family global regulator that regulates mo

The winter holidays are a time to celebrate, but can be oppressive for those who cannot. It is therefore important to look after trainees and colleagues who miss their loved ones on Christmas day. [Image: see text]

Residue interaction networks (RINs) provide graph-based representations of interaction networks within proteins, providing important insight into the factors driving protein structure, function, and stability relationships. There exists a wide range of tools with which to perform RIN analysis, taking into account different types of interactions, input (crystal structures, simulation trajectories,

Several enzymes from the metallo-β-lactamase-like family of lactonases (MLLs) degrade N-acyl L-homoserine lactones (AHLs). They play a role in a microbial communication system known as quorum sensing, which contributes to pathogenicity and biofilm formation. Designing quorum quenching (QQ) enzymes that can interfere with this communication allows them to be used in a range of industrial and biomed

The overall significance of loop motions for enzymatic activity is generally accepted. However, it has largely remained unclear whether and how such motions can control different steps of catalysis. We have studied this problem on the example of the mobile active site β1α1-loop (loop1) of the (βα)8-barrel enzyme HisF, which is the cyclase subunit of imidazole glycerol phosphate synthase. Loop1 var

The protein tyrosine phosphatase (PTP) SHP-1 plays an important role in both immune regulation and oncogenesis. This enzyme is part of a broader family of PTPs that all play important regulatory roles in vivo. Common to these enzymes is a highly conserved aspartic acid (D421 in SHP-1) that acts as an acid/base catalyst during the PTP-catalyzed reaction. This residue is located on a mobile loop, th

Some countries try to curb internationalisation in academia or require that foreign scientists take language courses. While this is done for the wrong reasons, learning the language of the host country has great benefits for academic staff. [Image: see text]

Noncovalent interaction networks provide a powerful means to represent and analyze protein structure. Such networks can represent both static structures and dynamic conformational ensembles. We have recently developed two tools for analyzing such interaction networks and generating hypotheses for protein engineering. Here, we apply these tools to the conformational regulation of substrate specific

The Alabama Supreme Court decision to consider embryos as children sheds light on a growing problem for IVF clinics: what to do with the increasing number of frozen surplus embryos? [Image: see text]

Protein tyrosine phosphatases (PTPs) are crucial regulators of cellular signaling. Their activity is regulated by the motion of a conserved loop, the WPD-loop, from a catalytically inactive open to a catalytically active closed conformation. WPD-loop motion optimally positions a catalytically critical residue into the active site, and is directly linked to the turnover number of these enzymes. Cry

Protein structure (and thus function) is dictated by non-covalent interaction networks. These can be highly evolutionarily conserved across protein families, the members of which can diverge in sequence and evolutionary history. Here we present KIN, a tool to identify and analyze conserved non-covalent interaction networks across evolutionarily related groups of proteins. KIN is available for down

Many grants from US funding agencies are restricted to US citizens or permanent residents which negatively impacts the career options for foreign scientists working in the USA. [Image: see text]

Practical advice for prospective graduate students on how to apply for a PhD position in the USA and Europe. [Image: see text]

The cellular imbalance between high concentrations of ribonucleotides (NTPs) and low concentrations of deoxyribonucleotides (dNTPs), is challenging for DNA polymerases when building DNA from dNTPs. It is currently believed that DNA polymerases discriminate against NTPs through a steric gate model involving a clash between a tyrosine and the 2'-hydroxyl of the ribonucleotide in the polymerase activ

Abandonment of diversity, equity and inclusion programs undermines fairness and the productivity of research.

Is scientific partnership between the UK and EU on the Horizon?

In the early 2000s, Tawfik presented his 'New View' on enzyme evolution, highlighting the role of conformational plasticity in expanding the functional diversity of limited repertoires of sequences. This view is gaining increasing traction with increasing evidence of the importance of conformational dynamics in both natural and laboratory evolution of enzymes. The past years have seen several eleg