A Brief Look at Heat Shock Proteins

Proteins are the metabolic workhorses of the cell; they engage in a variety of essential activities ranging from enzymatically catabolizing macromolecular food sources to serving as structural components that maintain cell stability. Maximizing protein function relies on intricate non-covalent interactions occurring on the secondary, tertiary, and quaternary levels that help determine the overall shape of the protein. In their native states, proteins will assume the most energetically favorable configuration. Occasionally however, cells are exposed to exogenous disruptions such as heat stress. Heat Stress can compromise protein three-dimensional structure. Hydrophobic residues tend to be buried in the interior of the protein but when

Aim 1: To identify Aha1 in the patients’ sample. From the medical center, metastatic and non-metastatic cancer patients’ tumor tissues along with buffy coat, plasma, serum, viable lymphocytes, as well as urine samples will be collected. Aha1 along with other secretory proteins such as Hsp90α, Survivin, MMP will be evaluated in cancer patients’ samples.

ATP stands for adenosine triphosphate. It is a coenzyme that cells use to store energy. Also ATP is present in all cell's cytoplasm and nucleus as well because it’s vital for proper life functions in plants and animals.

ATP serves as a cellular signal in the body as the cells use ATP to help them regulate. If a cell has enough ATP, the ATP signals the cell to store nutrients when there is enough ATP. It acts as an on-off switch to control chemical reactions and to transmit messages. The shape of the protein chains that produce the building blocks and other structures are determined by weak chemical bonds which are simply broken and reconstructed. These chains can lengthen, shorten and change shape depending on the input or output of the energy from ATP. The changes the chains modify these shapes of the protein and its function, making it become either active or inactive. Furthermore, the energy from ATP is used to pump The transmembrane ions across the cell

The core of the structure of the C-domain in whole DT is formed by eight β-strands forming two sheets of three and five strands, respectively. These two sheets are surrounded by six short α-helices6. The active site of the C domain is located in a cleft formed by three beta strands named CB2, CB3, CB7, a helix, CH3, and a loop, CL2. The loop CL2 including amino acids 32-54 which covers active site, becomes disordered from residues 39 to 46 upon binding of NAD7. This suggests a potential role for this loop in the recognition of the ADP-ribose acceptor substrate, EF-2. The ADP-ribosylation reaction has been proposed to proceed by a direct displacement reaction, with the pi-imidazole nitrogen of diphthamide being activated by Glu148 for nucleophilic attack on the N-glycosidic bond of NAD8. The loop of 14 amino acid residues linking the C domain to the T domain must be cleaved in order to activate DT9. More work is still needed to fully understand the mechanism of translocation of DT. The precise molecular and dynamic description of the contacts between the T and the C-domains, the cell membrane and maybe other cell components remain to be

The abundant amount of adenylate and creating enzymes acting at diffusion control limit would instantaneously process the most of ADP produced by ATPase reactions. The discussion of the ADP metabolism implies that ADP would barely act as negative feedback signal to ATP production due to the small amount of ADP diffusion.

ATP is a high-energy molecule that is broken down to form ADP so it can release energy. Phosphocreatine (PC) is also a high energy molecule, found in the muscle fibres. An enzyme known as Creatine Kinase is triggered when there is a breakdown of ATP, which results in a higher amount of ADP. As a reaction that occurs outside of the body, it provides the energy to resynthesise ATP at a steady and quick rate.

The hexameric p97 protein belongs to the type II AAA ATPase protein family and is conserved

The experiment is conducted to find out how the membrane is affected by different temperatures. Betalain pigment increases with high temperatures because most mammalian proteins denature and tertiary structure unravels because the strong covalent bonds between the R groups of amino acids in the polypeptide chains are destroyed at

Proteins are essential for cellular functions in all forms of life. Though proteins have been studied for decades, membrane proteins have not been properly understood due in part to their physical complexity and the difficulties in testing. Though many challenges hinder the discoveries in this area of biochemistry, Professor Alessandro Senes believes that the difficulties encountered only make the results more worthwhile. Researching these proteins advances our understanding of the importance of the protein structure on the molecular function in the cells. As Professor Senes and his team continue to explore recurring patterns in these membrane proteins, they further explore new topics in this growing area of science.

Polier et al. 2013 identified a new mode of action for ATP-competitive kinase inhibitors, is a significant class of anticancer agents, these inhibitors are used in the clinic (Polier et al., 2013). This discovery of new inhibitory mechanism of action exposes the interactions among the chaperone protein heat shock protein 90 (HSP90), its co-chaperone CDC37 (a scaffold protein) and the protein kinases that they regulate. However, the inhibition of Hsp90 in vivo cause in degradation of kinase clients, with a curative effect in dependent cancers. Result of this study shows that the Cdc37 binding to protein kinases is itself disturbed by ATP-competitive kinase inhibitors (vemurafenib and lapatinib). Polier et al used the commonly mutated BRAF kinase model to perform their investigations.

In this lab, we had learned how both temperature and pH affect the enzyme activity. We created a hypothesis and later tested them using 4 procedures. These procedures included test tubes, cuvettes, baths with different temperatures, thermometers, chemicals and spectrophotometers. We had created graphs to show a visual of the data we had collected rather than just simply showing numbers. Having a graph was very helpful, so we can better compare the data. This lab had helped us better understand enzymes.

The endoplasmic reticulum (ER) is an essential organelle that is a major place for the biogenesis of cellular components including proteins, lipids, and carbohydrates and internal calcium storage. ER is primarily responsible for protein translocation, protein folding and protein post modification. Proper folding of protein in the ER is accomplished with the aid of ER resident proteins or enzymes such as chaperones. Binding of chaperones to

In addition to the above uses of pyrazole as therapeutic agent, it has recently been recognized to have modulatory effect on UPR, especially for the treatment of cancers and other diseases. The benzyl pyrazole derivative HSF1A, a small molecule activator of HSF-1, was identified in a yeast-based high-throughput screen (72). Induction of chaperones by HSF1A was shown to reduce protein misfolding and aggregation-mediated toxicity in cellular and fly models of polyQ-related diseases, and to activate HSF-1 in Drosophila and mammalian cells without inhibition of Hsp90 activity or causing proteotoxicity. Rather, HSF1A was suggested to interact with the cytosolic TCP-1 ring complex (TRiC). This proposed mechanism of action is of interest as TRiC

Molecular chaperones stabilize unfolded or misfolded proteins until native conformations have been obtained to promote cell survival during and after stress conditions. They do not change or add to the folding principles encoded by a protein because polypeptide chains inherently carry within them all the information that is necessary for achieving the native state of a protein. Instead, they optimize the folding process by stabilizing folding intermediates and are involved in every aspect of proteome maintenance including de novo folding, refolding of stress-induced misfolded proteins, and targeting proteins for degradation (Hartl 2009, Hartl 2011). Chaperones, many of which are induced or upregulated only during stress conditions, work in cooperative networks when protein-aggregate concentration