Introduction Lipoprotein A was first discovered in humans by Kare Berg in 1963 whilst a study of variation in LDL antigenicity. The Human gene encoding lipoprotein(a) was cloned in the year 1987(1). Lipoprotein A Structure Lipoprotein A has a similar structure to the LDL molecule with the addition of a covalently bound specific apolipoprotein A (2). Apolipoprotein(A) is a homologue of plasminogen and contains several copies of KRINGLE 4 plasminogen, a single copy of KRINGLE 5 plasminogen and an inactive protease domain (2). Studies have indicated that the number of KRINGLE 4 domains can range from 51 to 12 giving rise to approximately 34 different apo(a) isoforms. Also,10 distinct types of KIV domains exist for the repeated KIV domains, …show more content…
Experiments showing that lysine analogues break down lipoprotein A assembly suggest that lysine binding domains in apo(a) and lysine residues in apo are involved in the primary non-covalent interaction.15. Mutagenesis studies show defective Lp(a) assembly after the removal of lysine binding sites in apo(a) KIV types 6–8 providing further evidence. A recent study of single point mutations introduced into the lysine binding sites in KIV 6–8 has shown that KIV 7 and 8 are essential for efficient lipoprotein A assembly (7). Multiple apoB sequences that noncovalently bind apo(a) are documented. An apoB lysine residue in the N-terminus, apoBLys680 mediating noncovalent binding of an apoB18 fragment to apo(a) have been postulated. Further evidence has shown that a peptide containing the apoBLys680 residue is bound to apo(a) KIV type 7. C-terminal moiety of apoB has also been hypothesized in the noncovalent interaction with apo(a). Truncated apoB molecules found in a region between apoB95 (4330 amino acids) and apoB97 (4397 amino acids) has been said to be important for efficient Lp(a) assembly. Characterisation of the apoB4330 to 4397 regions found a 21-amino acid sequence (amino acids 4372–4392) containing four lysine residues (including a highly conserved lysine at position 4372) that could be an a apo(a) binding site. A peptide spanning this
Reverend Dr. Lynda Marie Jordan is a native Bostonian, born in Roxbury Massachusetts. She is the third of less than fifteen women of African descent—to date— that has earned the Doctor of Philosophy (Ph.D.) degree in Chemistry, from the Massachusetts Institute of Technology (MIT). After receiving the Ph.D. degree, Dr. Jordan became a Postdoctoral Fellow at the Institut Pasteur in Paris France, where she made substantial contributions towards the purification and characterization of key proteins associated with human inflammatory processes. Her pioneering work of identifying both the calcium-dependent and calcium-independent high molecular weight Human Placental Phospholipase A2 (PLA2) isoforms contributed to the groundwork for the advancements
A protein has multiple existing structures, these are the primary, secondary, tertiary and quaternary structures which occur progressively. A protein is essentially a sequence of amino acids which are bonded adjacently, and interact with one another in various ways depending on the R group that the amino acid contains. There are 20 different amino acids which are able to be arranged in any given order, thus giving rise to a potential 2.433x1018 (4.s.f) different combinations, and therefore interactions between the various amino acids.
Molecular Cell Biology, 7th Edition, 2013, Lodish, Berk, Kaiser, Krieger, Bretscher. Ploegh, Amon, and Scott. W.H. Freeman and Company (ISBN-13: 978-1-4292-3413-9)
Figure 3. Protein expression and purification protocol is shown in the schematic in (A). To confirm expression of the P278L mutant, a western blot was performed. Note the presence of Kif5A in all fractions, and enriched in the E1 and E2 eluate.
It’s a part of the apoliprotein B-100 gene located in the HM487065 locus. APOB 100 produced in the liver and it is the building block very low-density lipoproteins (VLDLs), intermediate-density lipoproteins (LDLs), and low-density lipoprotein (LDLs). These molecules transport fats and cholesterol in the bloodstream (1). Further analysis such as the nucleotide alignment showed that most of the sequences are conserved, especially the TGATACAA sequence at the 68th -75th base. As moving down the list of the species, the sequences tend to have more deviations. The sequences of the Tasmanian devil, platypus, kiwi, bustard and turtle have fewer conserved nucleotides compared to the species listed above them. In addition, a phylogenetic tree was determined from the alignment. The tree showed that the sequences of human, gorilla, rhesus monkey, night monkey, and lemur are closely related to each other. As the tree branches out more, the resemblance between them decreases. The protein alignment of the same 14 species was also determined. The most conserved amino acids in all 14 species are glutamine, leucine, isoleucine, and tyrosine. These amino acids are required for basic cellular function so nature tends to favor them. Therefore, they are highly
This protein is found in endoplasmic reticulum and participates in the synthesis of cholesterol by catalyzing the removal of the 14alpha-methyl group from lanosterol. Various homologous genes are found in all three eukaryotic phyla, fungi, plants, and animals. All of these homologs indicates that this is one of the oldest cytochrome P450 genes. Similarly, two transcript variants encoding different isoforms have been found from previous studies for this gene. Multiple diseases are assonated with this gene. Mostly, related to some regulatory
However, a possible mechanism by which ApoE interact with tau proteins have been demonstrated. Paired helical filaments in NFTs often contain
There are many risk factors which facilitate the development of atherosclerosis; abnormal level of blood lipids is just one of them. Blood lipids consisted of three components including cholesterol, triglycerides, and two major forms of lipoproteins: high density lipoproteins (HDLs) and Low density lipoproteins (LDLs). In addition, one of the critical components which determine the degree of blockage on the arterial walls is the quantity of
The good form of this sterol in the body is your HDL, because it picks up all the bad form in your body and store it in the liver to be converted into the bile then exits out.
The Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (EPDETHBCA) (2001), made the low density lipoprotein (LDL) their primary target of therapy, which is the major cholesterol carrying lipoprotein particle in plasma, is primarily derived from lipoprotein particles made by the liver, as the levels of LDL cholesterol increase, the risk of developing CVD increases. An estimated of 13.8% of adults have total serum cholesterol levels ≥240 mg/dL (Go et al., 2014). Saturated fatty acid and trans fatty acid intakes tend to increase LDL, which are the strongest dietary causes of elevated LDL concentrations (Lichtenstein, Ausman, Jalbert & Schaefer, 1999). The increase LDL cholesterol and reduce high density lipoprotein (HDL) cholesterol, cause endothelial damages which is the first stage in the development of atherosclerosis and may cause thrombosis afterwards (Thomas et al., 2007). Inflammation under lies atherosclerosis can be influenced positively by anti-inflammatory diet (Thomas et al., 2007). Independent of
Type Ⅲ mutations: mutant which is characterized by the LDL receptor gene can be synthesized to the cell surface, but can not bind to the ligand.
While cholesterol is a commonly used word in healthcare, most people do not know what it means. Cholesterol is a “fat-soluble steroid alcohol that is produced in the liver from saturated fats and obtained from animal fats and oils in the diet” (Wells, 2012). Cholesterol is used to make certain hormones, like estrogen and testosterone, and aids in digesting fats. Cholesterol is a combination of a steroid ring structure and a hydroxyl group (Figure 1). It is important to note that there are two types of cholesterol: LDL, which is low-density lipoprotein and HDL which stand for high-density lipoprotein. LDL is considered the “bad cholesterol” because it contributes to fatty buildup in the arteries which can later lead to heart disease or a
The position of His57 is assisted by Asp102. Ser195 becomes a powerful nucleophile that attacks the carbonyl carbon of the target protein in a nucleophilic attack. A tetrahedral intermediate is formed, stabilised by the presence of an Oxyanion Hole that forms hydrogen bonds with the negatively charged oxygen atom above the serine residue. It is usually made up of positively charged amines, such as Gly193. The tetrahedral intermediate then collapses and the acyl-enzyme is formed, resulting in the release of an amine.
Campbell and Farrell define proteins as polymers of amino acids that have been covalently joined through peptide bonds to form amino acid chains (61). A short amino acid chain comprising of thirty amino acids forms a peptide, and a longer chain of amino acids forms a polypeptide or a protein. Each of the amino acids making up a protein, has a fundamental design that comprises of a central carbon or alpha carbon that is bonded to a hydrogen element, an amino grouping, a carboxyl grouping, and a unique side chain or the R-group (Campbell and Farrell 61).
Omega-3 fatty acids are essential fatty acids which possess the most potent immunomodulatory activities. It is also known as long-chain polyunsaturated fatty acids (PUFAs), which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (1). They are united in different parts of the body containing cell membranes and play a crucial role in anti-inflammatory processes and in the viscosity of cell membranes (2-3). EPA and DHA are also the precursors of several metabolites that are strong lipid mediators. Many scientists believe that omega-3 fatty acids are beneficial in the prevention or treatment of several diseases are characterized by an increased level of interleukin 1 (IL-1) such as Coronary heart diseases, cancer and AAA (4).