Nov. 25, 2019
Since the mid 20th century, chemotherapy has become prominent as one of many classes of cancer therapy. Many chemotherapeutic drugs, such as bleomycin, work by preventing cancer cellular division. Specificity is often a challenge to this end, and many patients who undergo chemotherapy also experience side effects resulting from chemotherapeutic drugs attacking normal, non-cancerous cells. For instance, bleomycin works by binding to the DNA of cells and preventing further synthesis by breaking its strands. Shown here is bleomycin (PDB ID 1EWJ), a compound first discovered in Streptomyces verticillus by Hamao Umezawa in 1966. It is being transported by bleomycin-binding protein.
Nov. 18, 2019
Neurexin and Neuroligin are two proteins that are important for the formation of neural synapses (PDB ID: 3VKF). When bound to neuroligin, neurexin kicks off the formation of a vesicle transportation network in the pre-synaptic cell. Through alternative splicing, neurexin can selectively bind to different neuroligins, allowing for the creation of unique neural network architectures. Deletions and mutations in genes encoding neurexin have been associated with neurological conditions such as autism, schizophrenia, and Tourette's syndrome.
Nov. 11, 2019
Avidin is a protein found in the egg whites of various bird species. It is remarkable for its ability to bind a molecule called biotin – commonly known as Vitamin B7 – extremely tightly. With a dissociation constant of around 10-14 mol/L, the interaction between biotin and avidin is the single strongest known interaction between a protein and its ligand and is among the strongest noncovalent interactions in nature. It is theorized that avidin has an antibiotic effect in the egg. Bacteria require biotin to grow, and by tightly binding any biotin, avidin makes it much more difficult for bacterial colonies to survive. This theory is supported by the existence of another avidin-like protein in Streptomyces avidinii called streptavidin, which S. avidinii uses like an antibacterial weapon to slow the growth of competing bacteria. Due to their exceptional biotin binding strength, both avidin and streptavidin are widely used in biochemical science. The first video shows the structure of an avidin monomer with a bound biotin. The second shows the binding pocket of biotin on avidin, with its shape (shown as a surface) nearly perfectly optimized to the shape of biotin (shown as a series of floating surface points. PDB ID: 2AVI)
Nov. 4, 2019
Many people are aware of thyroid diseases such as Grave’s disease, hyperthyroidism, and hypothyroidism, but don’t understand the disease state fundamentals. For most thyroid related diseases, the problem lies with either the over-secretion, or lack thereof, of the two hormones triiodothyronine (T3) and thyroxine (T4). This week we will focus on thyroxine, the prohormone of triiodothyronine. Aiding in almost every bodily function, the synthesis of thyroxine by the thyroid is crucial to the survival and normal function of a human. For example, when the body does not produce enough thyroxine, a condition commonly known as hypothyroidism, an individual may experience lethargy, slurring of speech, slowing of movement, weight gain, and constipation. For all these processes to function normally, they require triiodothyronine, but that active hormone can only exist if there is already the prohormone thyroxine present to convert. PDB ID: 2CEO
Oct. 28, 2019
Carnitine palmitoyltransferase II (CPT II) deficiency is a condition that prevents certain fats from being used by the body for energy production. This rare metabolic disorder has three presentations - lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form. The first two are severe forms of the disease characterized by liver failure, low sugar and ketone levels, weakened heart, and early death. There have been 18 and 30 cases identified, respectively. The myopathic form one is the milder form of the disease and is characterized by exercise-induced pain. Only 300 cases have ever been reported. CPT II disorder occurs due to the mutation in the CPT II gene. This gene contains the information for making carnitine palmitoyltransferase 2 protein (PDB ID: 2H4T), a key enzyme for fatty acid breakdown. In normal cells, fatty acids are attached to carnitine before entering the mitochondria. Inside mitochondria, the carnitine is removed, and a coenzyme A is added by CPT II enzyme. This step is key in fatty acid oxidation! Without it, fatty acids cannot be metabolized.
Oct. 21, 2019
Cyanea nozaki is commonly referred to as the Ghost Jellyfish because of its ghostly appearance. Its epidermis is cream-colored and bell-shaped with a flare at the bottom where there are several layered lobes. It has a hundred or more translucent tentacles emerging from the bell-opening that stretch more than 30 feet. The Ghost Jellyfish floats through the water like a fog in the wind - very eerie indeed! Not to mention that it may live for thousands of years. Here is the ghostly crystal structure (PDB ID: 4NQG) of Ca(2+)-regulated photoprotein mitrocomin from the outer bell of another cnidarian with a ghost-like characteristic - luminescence. 👻
Oct. 15, 2019
In 1996 the Nobel Prize in Chemistry was awarded to three researchers for their contributions to the discovery and synthesis of Fullerenes (PDB ID 5HKN). This class of molecules was theorized to exist in deep space before it was synthesized in 1985. The name was inspired by the eccentric visionary architect Buckminster Fuller who used the sphere as a central architectural component due to it's stability and volume to surface area ratio. Since it's synthesis in 1985, these molecules have been under intense investigation for their potential medical applications ranging from drug-delivery and bio-imaging to cancer therapy. C60 (the 60 carbon atom Fullerene) is the largest molecule shown to exhibit wave-particle duality (a phenomenon which all things theoretically exhibit).
Oct. 7, 2019
Clostridium tetani is a rod-shaped bacterium known for causing tetanus - a bacterial infection characterized by muscle spasms. Tetanopasmin is a potent neurotoxin (shown here, PDB ID: 5N0B) released by C. tetani spores as they grow and mature. If an open wound is exposed to these spores, tetanopasmin can travel through the bloodstream and eventually reach the nervous system. Once there, Tetanopasmin attacks the body by blocking key inhibitory neurotransmitters at motor nerve endings. This inhibition causes muscle spasms (typically beginning with lockjaw) as well as fever, headache, and high blood pressure. Due to its high potency, exposure to tetanopasmin will not allow you to build immunity, as an immune response would require more than a lethal dose of the toxin. Fortunately, for prevention, an inactivated form of tetanopasmin is used for vaccination.
Sept. 30, 2019
Leeches have long been used in medicine to increase blood flow. This works because their saliva contains an enzyme known as hirudin (pictured here. PDB ID: 1A3B). This enzyme acts as an anti-coagulant - both dissolving pre-existing clots and preventing future clots due to its inhibitive activity on pro- clotting factors such as thrombin and fibrinogen. Leech therapy (hirudotherapy) is commonly used as a solution for patients with varicose veins, who commonly experience venous congestion or coagulation. It's also useful for patients who have undergone reconstructive surgery and require improved blood flow to the area.
Sept. 23, 2019
X-Ray Crystallography is no easy process, and it has its limitations as we've previously described in one of our blog posts [http://ow.ly/qN0150w4fQJ]. A big challenge stems from the inconsistencies during phasing resulting from X-ray absorption artifacts that lead to inconsistent sampling of crystals. One of the ways scientists have attempted to solve this issue is by strategically processing the proteins as they experience radiation damage and then relying on powerful software to identify the resulting defects and revert the changes. Shown on the top left is a radiated sample of Bovine Trypsin (PDB ID: 1n6y). This is one of the first protein structures to be tested using the technique known as Radiation-damage Induced Phasing method (RIP). The image on the bottom right is for comparison. This is PDB ID 1s0q which is Bovine Trypsin imaged using x-ray crystallography.