In eukaryotes, DNA replication is initiated when two ring-shaped hexameric helicases load at defined DNA sites, called origins, and engage one another in a head-to-head arrangement. Acting as a double hexamer, they open the origin duplex and set up two divergent replication forks, exposing the single-stranded templates that replicative polymerases require. To define the structural…
Type 2 diabetes mellitus (T2DM) remains a major global health challenge, with many patients failing to achieve optimal glycaemic control despite the availability of established therapies. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which catalyzes the local regeneration of active cortisol, represents a promising therapeutic target for addressing the multifactorial nature of metabolic disorders. This…
Nitrilases are enzymes that convert nitriles to the corresponding carboxylic acids and ammonia or to the corresponding amides. They have substantial sequence homology to the cysteine-dependent amidases, which convert amides to the corresponding carboxylic acids and ammonia, but the nitrilases do not convert amides. Unlike the amidases, for which there are many crystal structures, nitrilases…
Human DCAF1 is a multidomain protein that plays a critical role in protein homeostasis. Its WDR domain functions as a substrate recruitment module for RING-type CRL4 and HECT family EDVP E3 ubiquitin ligases, enabling the ubiquitination and proteasomal degradation of specific substrates. DCAF1’s activity has been implicated in cell proliferation and is documented to promote…
The cytoskeleton in cells can play mechanical and transportation roles. Such networks, when confined, have properties that are not like that of bulk networks. We show how a self-consistent field theory approach allows the calculation of density and polarisation density profiles within a confined space, and associated prediction of mechanical properties [1]. We also contrast…
Transient Protein-Protein Interactions (PPIs) are central mediators of protein activity and signaling network and their modulation has significant impact on cell metabolism and regulation. They are therefore considered promising, albeit challenging, opportunities to expand druggable chemical space. However, due to the transient nature of these interactions, this class of PPIs is particularly challenging to characterize…
Quantum biology is an exciting field of research with a pronounced interdisciplinary focus. This lecture will cover a short history of quantum biology before clarifying some of the important concepts in the field and reviewing the different biological contexts in which quantum effects may play a role, which include photosynthesis, enzyme catalysis, DNA mutation, receptor…
HIV-1 protease is a critical enzyme for viral maturation and one of the most well-studied proteins in structural biology. While much attention has focused on its active site, there is interest in how the enzyme might interact with small molecules at other regions on its surface. In particular, some of these potential sites, called cryptic…
