Feb. 10, 2020
With the ongoing outbreak of 2019 novel coronavirus, many are quick to remember the spread of Sudden Accute Respiratory Syndrome (SARS) coronavirus that was identified back in 2003. SARS is a more lethal but less infectous type of coronavirus that also started in China, with cross-species infection to humans starting in animal markets. The SARS virus was quickly controlled largely due to public awareness and containment efforts, but perhaps most unprecedented was the amount of collaboration between scientists and researchers around the world at the time, which enabled the identification of the causal agent and genetic sequencing to be accomplished within weeks of the outbreak. Shown here is SARS coronavirus replicative protein NSP9 (PDB ID: 1QZ8), which plays a role in SARS coronavirus replication.
Feb. 3, 2020
You've probably heard a lot about coronavirus lately with the latest infection in Wuhan, China. Coronaviruses are a group of viruses that cause upper respiratory infection in mammals (including humans) and birds. These viruses are envelope viruses with a single-stranded RNA genome. All of us in the scientific community are racing to find a rapid response in the form of a vaccine or treatment. Researchers have identified viral protease M as a potential target for treatment to stop the spread of the virus. Retroviral proteases are enzymes that are vital to the spread of retroviruses such as leukemia viruses and HIV. Not all viruses encode a protease, but those that do ensure that proteolytic action occurs at the proper time and place, independent of a host. In general, these viruses have polyproteins that are cleaved by the viral protease(s) during replication and assembly. Proteases are also involved in mediating virus assembly/disassembly by converting uncleaved, assembled polyproteins into mature capsids capable of disassembling upon virus entry into a newly infected cell. All of these events serve to optimize infection by the virus. Shown in this post is a homology model of the 2019-nCov coronavirus protease created by Innophore [https://innophore.com/2019-ncov/]
Jan. 27, 2020
Collagen is a molecule we’ve discussed before (https://www.instagram.com/p/Bs6Vl-ihArM/). As mentioned, there are 29 versions of collagen – each with unique functions. This week’s #motw is the Pro-Pro-Gly 10:3 triple helix collagen molecule (PDB ID: 1K6F). Many collagen molecules exhibit a PPG motif with various other residues dispersed throughout the sequence. It’s due to this motif that collagen molecules form triple helical tertiary structures and stick to other collagen molecules like “glue”. In fact, the word collagen comes from the Greek word “kólla” which means glue. Fun fact: as we age collagen production and quality reduces in our bodies, but good nutrition helps maintain levels and improves quality.
Jan. 20, 2020
Many proteins targeted by therapeutics are surface proteins. They present on the phospholipid bilayer of cells. These proteins weave in and out of the cell across this layer. The portions of the protein exposed to the bilayer are very hydrophobic and make excellent binding sites! Therefore, when testing whether your therapeutic binds in an ELISA [http://ow.ly/c2Ga50xKJRl] test, you may have false positives because the therapeutic attaches to these hydrophobic portions. Enter the nanodisc (PDB ID: 6CCH). These are mock phospholipid bilayers! The lipids are trapped in between two membrane scaffolding proteins you see here in blue. Surface proteins will naturally stabilize in the bilayer and present just as they would on the cells surface! These nanodiscs have the advantage of assisting solubilization of target proteins and mock the native environment of liposomes.
Jan. 13, 2020
A proliferation-inducing ligand (APRIL, PDB ID: 1U5Z) is a member of the tumor necrosis factor (TNF) superfamily and plays a role in B cell maturation and generation. The specific role of APRIL in B cell development is not fully understood. However, in contrast to other TNF-ligands, it was discovered that APRIL has shown to promote the survival of tumor cells in tissue culture. The expression of APRIL has been correlated to the prognosis of B cell malignancies, with a high expression of APRIL showing a somber prognosis. APRIL could potentially be used as a therapeutic biomarker to determine the severity of B cell malignancies, providing a guide for effective treatment planning. Targeting and reducing the expression of APRIL would allow apoptosis of malignant cells, since APRIL would not be present to protect malignant cells.
Jan. 6, 2020
Calcium-modulated protein (calmodulin) is a eukaryotic protein whose main significance is its calcium-binding properties. Calmodulin is mostly found in cells' cytoplasm and interacts with numerous other cell proteins. It regulates and affects many cellular functions, such as fertilization, contraction of muscles, and intercellular signaling. Calmodulin is highly important to healthy eukaryotic life. Mutated calmodulin-encoding genes or damaged calmodulin-binding sites lead to calmodulinopathies – life-threatening arrhythmia syndromes which often result in sudden cardiac death.
Dec. 30, 2019
Holidays are a time filled with fun and food. The hormone oxytocin (one of our more popular posts http://ow.ly/QtVA50xHah0) is responsible for the feeling of joy, but not everything during the holidays is enjoyable! Financial pressure, crowds and traveling counter the good effects of oxytocin. Cortisol (PDB ID 6HGF), the main stress hormone, is activated when the body is under stressful conditions. This hormone can increase your sugar production which causes high blood pressure. It is also responsible for altered immune system responses which in colder climates leads to increased risk of contracting the flu. Let this serve as a friendly reminder from Macromoltek to take it easy for the holidays. You may be paying for it later.
Dec. 23, 2019
Azotobacter vinelandii is a special type of bacteria called a diazotroph. These bacteria fix atmospheric nitrogen gas into stable forms that are deposited into soil. A. vinelandii accomplishes this feat using an enzyme called a nitrogenase (PDB ID: 5N6Y) which has molybdenum iron-sulfido clusters that act as active sites. The clusters bind to nitrogen which is then fixed to hydrogen to make ammonia. In turn, plants take up the nitrogen which is a major component of chlorophyll. Without chlorophyll, plants couldn't absorb light for photosynthesis and the entire ecosystem of the planet would collapse!
Dec. 16, 2019
Life as a tomato plant is not an easy one. Insects such as butterflies and moths (order: Lepidoptera) constantly gnawing at your leaves and you have but one option - to fight back. Thankfully, an enzyme by the name of threonine deaminase (TD) allows just that. TD (shown here, PDB ID: 1TDJ) normally functions by catalyzing the reaction of threonine into alpha-ketobutarate and ammonia, a vital step in amino acid synthesis. However, when this enzyme is eaten by lepidopterans, it becomes unregulated and able to continuously break down threonine in the gut of an insect, while also creating ammonia - a toxin for these insects. This produces a threonine deficiency, limiting necessary nutrients, and prevents these insects from harming tomato plants ever again.
Dec. 2, 2019
Cancer is a disease where abnormal cell growth occurs unregulated and will often form into a mass. Living organisms have a protein that helps regulate cell growth to prevent cancer. P53, or the tumor suppressor, is this protein. If for any reason DNA is damaged, p53 activates and holds the cell in cell cycle arrest. This stops the cell from dividing until the DNA is repaired. If the DNA cannot be repaired it will then initiate apoptosis, which is the death of the cell. Thus it cannot divide and pass on the mutated DNA. Having reduced levels of p53 can increase your odds of developing cancerous tumors. A way to regulate this is by using Mdm2 (Pictured here. PDB ID: 2MWY) another protein that binds to p53 to regulate levels of p53.