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Are you having trouble falling asleep? It may be worth learning a bit about the hormone melatonin. This hormone is a crucial participant in the regulation of the circadian rhythm.[1] The synthesis of this chemical follows the same path as that of serotonin with a few extra steps (see MOTW for 2/18/19). Once serotonin is made, serotonin N-acetyltransferase modifies the chemical into N-acetylserotonin.[2] Next, the synthesis of melatonin takes place via methylation of the hydroxyl group of N-acetylserotonin through the help of Hydroxyindole O-methyltransferase and S-adenosyl methionine.[2] Some common disorders treated with melatonin are insomnia, delayed sleep phase syndrome, and even jet lag, all of which are caused by sleep-wake cycle disturbances.[3] Using melatonin, an individual can reset their "internal clock" and reestablish a proper circadian rhythm. The rise and fall of melatonin levels are directly correlated with light exposure, a phenomenon known as the dim-light melatonin onset.[4] Blue light from computer and phone screens disrupt DLMO. Normally, in the morning melatonin production and secretion is relatively low. As night falls, melatonin production and secretion pick up and prepare your body for rest. So if you're having trouble sleeping, you may want to consider limiting screen time before going to sleep. PDB 1B6B

Summer is fast approaching – and here in Texas, that means scorpion season. Texas is home to a few scorpion species, with the most widespread being the striped bark scorpion, Centruroides vittatus. In winter months, scorpions are known to find warm, dry spaces to hibernate and avoid the cold weather. Oftentimes these spaces are inside the walls and attics of houses, so when temperatures rise – and scorpions become active again – it doesn’t take long for people to notice. While some of their cousins have stings, which can be occasionally fatal, serious reactions to striped bark scorpions are rare. Most stings are due to walking barefoot outdoors or accidental contact inside homes and are about as painful as a bee sting. Most stings can be avoided by simply watching where you step and wearing gloves when doing yard work. Pictured is one of the small proteins injected with the scorpion’s venom. PDB 6B9W

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin are widely used every day to decrease pain and inflammation. They inhibit the enzyme cyclooxygenase in order to reduce prostaglandin production, a compound responsible for inflammatory responses. Aspirin, unlike ibuprofen, has also been found useful in preventing heart attacks. Aspirin irreversibly binds to the enzyme and reduces platelet aggregation (blood clots) when taken. Shown is the crystal structure of aspirin with COX-2, an isoenzyme of cyclooxygenase (PDB ID: 5F19).

Dysentery is an intestinal disease that plagues developing countries and has had a major part in history – even deciding the outcome of multiple battles. Some examples include Napoleon’s Grande Armee being halted during the invasion of Russia and the Mexican Army losing the Battle of San Jacinto. In fact, the 1700s and 1800s saw massive outbreaks in the Western World. An article [1] from Science Daily claims 90% of all deaths in Sweden were due to dysentery during the worst outbreaks. This disease is the result of bacterial, viral, or parasitic infections often from contaminated food or water. These infections each have their own mechanism, but all cause damage to the intestinal lining which results in inflammation. This, in turn, leads to abdominal pain, spasms, cramping, edema, and further tissue damage due to the body's own chemical response. Treatment depends on the infection, so a common approach is a drug cocktail including amoebicidal drugs, antimicrobial drugs, and antibiotics. In less severe cases, allowing the infection to run its course is the best approach. This often in tandem with fluid maintenance. Pictured here is PDB 3NV9 – an enzyme Entamoeba histolytica uses to attack the intestinal lining. [1] University of Gothenburg. "Dysentery epidemic killed many in the 1700s-1800s." ScienceDaily. ScienceDaily, 25 October 2012. http://ow.ly/N0Vl30o7ClR

Opioid receptors are a class of proteins found throughout the brain and central nervous system with opioids (such as morphine) as ligands (shown here). These receptors are responsible for analgesia, or reducing the feeling of pain. The receptors undergo a conformational change upon binding to their ligand, causing the release of neurotransmitters involved in the transmission of pain. Because of this release, opioids are prescribed to treat pain, but prolonged use causes the effects to lessen because of the reduced interaction between receptor and ligand, thereby requiring more to get the same relief, causing the body to develop dependence and lead to addiction. Symptoms of addiction include uncontrollable cravings and inability to control opioid use and leads users to seek illegal opioids such as heroin. Overprescription of legal opioids has led to the current opioid crisis, including opioid abuse and related overdoses. PDBID: 4DKL

Now that spring break is approaching and many of us are considering hot, tropical destinations for our spring break vacations, we must think about heatstroke. Our bodies need to manage heat gain (and, in cold weather, heat loss) from the environment to maintain a core temperature that's normal - approximately 98.6 F (37 C). Whether sunbathing on a warm beach in the Caribbean or under the hot sun at a concert, our bodies cool themselves mainly by sweating. The evaporation of sweat regulates body temperature by absorbing heat and carrying it away. However, when exercising strenuously or otherwise overexerting in hot, humid weather, sweating is less efficient. Besides hot weather and strenuous activity, other causes of heat exhaustion include dehydration, alcohol use, and overdressing. Heat shock proteins (HSP) are a family of proteins that are produced by cells in response to exposure to stressful conditions. They were first found in relation to heat shock, but it is now known that they play an important part in other stress events like wound healing and even cancer! Shown here is the structure of Human MC-HSP90 in P21 space group (PDB ID: 3Q6N). It functions as a dimeric molecular chaperone found om metastatic cancer.

The adaptive immune system is the body’s defense force against foreign invaders, toxins, and cancer cells. Cancerous cells present a unique challenge because they contain antigens that make them easily confused with normal body cells. Cytotoxic T Lymphocytes (CTLs) are specialized cells that recognize and destroy cancerous cells. They are interrupted by CTLA-4 (“the breaks”) which downregulates the immune response and prevents a widespread attack against all cells. Ipilimumab is a monoclonal antibody that targets CTLA-4, effectively removing the brakes, and re-activates the immune system’s fight against cancer. An example of cancer for which ipilimumab is often used is metastatic melanoma. The pictured complex (PDB: 5TRU) shows the structure of Ipilimumab when bound to human CTLA-4 (lime colored).

Feeling sad, tired, and anxious? Well perhaps your serotonin levels are low. Serotonin has become popularly recognized as a “happy” molecule. It is synthesized within the GI tract’s enterochromaffin cells, where the amino acid tryptophan interacts with tryptophan hydroxylase to create 5-hydroxytryptamine(5-HT). After a simple decarboxylation of 5-HT, Serotonin is formed and ready to help improve mood, energy levels, and appetite! Some of the most popular commercial antidepressants directly influence serotonin levels and are termed SSRIs (Selective Serotonin Reuptake Inhibitors). These drugs work by inhibiting the body’s natural reuptake methods of serotonin, allowing for the neurotransmitter to stay in the system longer and in greater quantity. However, there are also natural ways to improving serotonin levels such as exercising and having proper exposure to sunlight.[1] PDB ID: 3BRN. Ref: [1]Young SN. How to increase serotonin in the human brain without drugs. J Psychiatry Neurosci. 2007;32(6):394-9.

Valentine’s Day is upon us, and along with it comes the concept of love. Researchers have pinpointed the body’s perfect recipe for love: Dopamine and #Phenylethylamine (PEA). PEA is shown in yellow in this crystal structure taken from a fly (PDB: 5GI6). It is the chemical responsible for that euphoric feeling we get when we fall in love. You know the kind: the butterflies in your stomach, the “warm fuzzies”, first date jitters. As it turns out, PEA is an amphetamine that triggers the release of dopamine in the body, so it is no wonder that people feel so good when they fall in love. If you don’t have a special someone this Valentine’s Day, don’t worry; you can get plenty of PEA from chocolate. So be sure to stock up as soon as it goes on sale!