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A norovirus outbreak recently struck some of the California wildfire shelters, causing several people to be quarantined. Norovirus is the primary cause of acute viral gastroenteritis, which can cause symptoms such as diarrhea, vomiting, and stomach pain. This virus is very contagious and easily spreads from person to person in confined places like the shelters. People become infected when they encounter any contaminated consumable, surface, or other’s hands and bring the contamination to their mouth. It’s necessary to thoroughly wash hands and surfaces during an outbreak. Shown is the norovirus 3C-like protease (PDB: 1WQS), an enzyme crucial to the replication of the virus. Though there is currently no vaccine, inhibition of this enzyme has been a proposed anti-norovirus therapeutic.

Tuberculosis is caused by a bacteria called Mycobacterium tuberculosis. Although it is a treatable disease, more than 2 million people die every year from lack of access to medicine or the rise of drug resistant strains. There are many proteins suspected to be involved in drug resistance and finding new therapeutic targets from them is vital in finding new cures. One cluster of proteins is referred to as antigen 85, containing three variations - A, B, and C. All three are secreted into the phagosomal space in the bacterial cell wall, interacting with fibronectin, reducing phagocytosis, and promoting infection. Antigen 85B is a promising target shown here in a structure that has lead to new insights into how the bacteria functions and discovery of new therapeutic targets. PDBID: 1F0N.

We all love chocolate, but is it good or bad for you? Some studies have shown that dark chocolate improves peripheral artery disease. These results are due to cocoa which is a polyphenol‐rich nutrient – a type of nutrient that elicits artery dilatation by reducing oxidative stress and increasing nitric oxide generation. Another study examined the association of chocolate consumption with insulin resistance and serum liver enzymes (pictured; PDB ID 3dnk*). This study concluded, that there is an inverse relationship between daily chocolate consumption and levels of insulin, HOMA-IR, and liver enzymes in adults, suggesting that chocolate consumption may improve liver enzymes and protect against insulin resistance. Even though studies have shown that chocolate is good for you, moderation is always key! Remember that dark chocolate is better than milk chocolate because of sugar to cocoa ratios.

The pungent bite of horseradish is familiar to most. Horseradish, along with its cousin wasabi, are used for their effects in condiments and dishes the world over - but horseradish has an important role that most people have never heard of. Enter horseradish peroxidase (HRP). HRP is a metalloenzyme (meaning it carries a metal atom to help it do chemistry) which uses hydrogen peroxide to induce a chemical change in a variety of substrates. This protein, found in high concentrations in horseradish roots, is vital to laboratory science - especially in the context of a test called ELISA. In this test, an antibody chemically linked to an HRP molecule is added to a solution, and allowed to bind to a protein-coated surface. A chemical marker is then added to the solution. This is where HRP comes in: if the antibody successfully bound to the surface, the attached HRP will begin to process the chemical marker, inducing a color change. After a certain amount of time, the reaction is stopped with a strong acid or base, and the color change is measured. More color change in the given timeframe corresponds to more HRP-antibodies bound to the surface. This, in turn, tells you how strong the interaction is between your antibody and the surface-bound protein! ELISA tests are used in labs that study proteins, but they are probably familiar to most people as the tests used to detect diseases like HIV in the bloodstream. Thanks to horseradish for doing its part to fight disease!

Platypus milk may be exactly what we need to fight against antibiotic resistance. The platypus is one of few known monotreme species in the world. Monotremes are a small family of mammals that can lay eggs and produce milk for their young. Platypus milk is unusual since it's exposed directly onto the parent's belly, meeting the outside world before being delivered to the child. To prevent harmful effects from external bacteria, the milk contains antimicrobial proteins that kill or disarm these microorganisms. Shown here is one of these antimicrobial protein folds dubbed the "Shirley Temple," due to its ringlet structure (PDB: 4V00), by researchers at the Commonwealth Scientific and Industrial Research Organization (CSIRO). Finding ways to utilize the antimicrobial proteins in platypus milk may be the key to counteract continuously emerging antibiotic resistance in infectious agents.

Dysregulation of glucocorticoid receptor (GR)-mediated signaling has been implicated in therapy resistance across a wide spectrum of cancer types. While the first GR antagonist mifepristone is being clinically evaluated, the search for more potent and selective small molecules continues. A recent publication presents a novel GR antagonist - ORIC-101- with better pharmaceutical properties, including reduced AR agonism. The graph presented at the attached link shows GR binding to ORIC-101 (PDB ID: 6dxk).

Transcription factors are a class of proteins known for their role in controlling/regulating the rate of transcription of genes. Genetics aside; transcription is the process by which DNA is made into messenger RNA (mRNA-the molecule responsible for translation of proteins). Clearly, without transcription, no protein would be synthesized! Thus, transcription is a major component of what makes you and all living things tick. Additionally, controlling the rates at which transcription occurs is important. Which brings us to the specific transcription factor known as Nuclear factor 2 (NRF2) pictured here (PDB: 3WN7). NRF2 is responsible for the control of hundreds of genes that have a wide range of capabilities, including the activation of many anti-oxidant genes like glutathion S-transferase (GST), which is capable of deactivating pro-carcinogenic agents and transforming them into less reactive water-soluble conjugates. You read that right; it helps you flush pro-carcinogens from your body! To learn more about interesting molecules and about our molecular modeling capabilities follow us on Instagram.

Many of the foods we eat contain a large number of polysaccharides. These molecules go through many metabolic processes within us to produce glucose. The glucose is then transported from the extracellular space into cells where it is used to generate ATP- which is the energy that our bodies use to carry out work. The real trick here is getting glucose through the cell membrane. Two important molecules play a role in this process. The first is insulin which is released from pancreatic Beta cells when there is an increase in glucose concentration. The second is the insulin target receptor (pdb:4ZXB) and this week’s featured molecule; Insulin Receptor (IR). IR is a subtype receptor of the tyrosine kinase family, which is also activated by IGF-1 and IGF-2. Once insulin binds to IR a cascade of events occurs via the PI-3K signaling pathway which causes the insertion of GLUT-4. GLUT-4 is the glucose transporter that walks glucose across the cell membrane. As you can see, insulin receptor is very important and errors in the receptor or the signaling pathway can be fatal if not treated promptly. A common pathology that causes problems with this pathway is diabetes mellitus type 2. In this form of diabetes there is an insulin resistance to some of the IR in the body. Patients with type 2 diabetes suffer from an elevated plasma glucose level which may lead to glycosuria and ketoacidosis. Treatment for type 2 diabetes involves an individual making lifestyle changes, self-monitoring blood glucose levels, and taking certain medications.

We first discussed the Ebola Virus on our Instagram back in 2016 ( http://ow.ly/yxpC30lWRPM ). At the time, the disease was making headlines due to an outbreak that began in 2014 which was the deadliest in history. There are still no antiviral drugs nor vaccines that have been approved for Ebola, but there is a treatment that entered phase I clinical trials as of March of this year (2018). The treatment is a monoclonal antibody (mAb) – an antibody that has been cloned from a unique parent cell – known as mAb114. It was isolated from a human survivor of the 1995 Ebola outbreak in Kikwit, Democratic Republic of the Congo. Thus far, the antibody has been shown to protect primates from a lethal injection of Ebola days after infection. The phase I trial is investigating whether varying doses of the treatment are safe for humans. As we mentioned in our previous post, the Ebola Glycoprotein (picture here, PDB: 5JQ3) was an excellent candidate to design a treatment and this is the very protein to which mAb114 binds.

Plants contain cells with walls constructed from a molecule called cellulose. Cellulose is an insoluble dietary fiber for us humans which is why we don't make dinner salads out of just any leaves and grass - we can't derive any nutrients from it! It takes a specialized organ that only ruminants have to digest the molecule. The organ, which the phylogenetic suborder derives its name, is called a rumen. The rumen is host to a diverse microbiome which ferments the plant matter to extract nutrients from cellulose. The bacteria in this microbiome use the pictured dockerin (RSCB 5LXV) to degrade carbohydrates and share the results with their host.