Search results

Porphobilinogen deaminase (HMBS) belongs to the hydroxymethylbilane synthase superfamily. HMBS is a cytoplasmic enzyme found in the heme synthesis pathway. HMBS is the 3rd enzyme of the heme biosynthetic pathway and catalyzes the head to tail condensation of 4 porphobilinogen molecules into the linear hydroxymethylbilane. HMBS gene mutations cause errors in pyrrole metabolism which in turn lead to the autosomal dominant disease acute intermittent porphyria.

Killer-cell immunoglobulin-like receptors (KIRs), are a family of cell surface glycoproteins found on Natural Killer (NK) Cells, which are important cells of the immune system. They control the killing function of these cells by interacting with MHC class I molecules, which are expressed on all cell types. This interaction allows them to identify virally infected cells or tumor cells that have a distinctive low level of Class I MHC on their surface. The majority of KIRs are inhibitory, which means that their recognition of MHC suppresses the cytotoxic activity of their NK cell. Only a limited number of KIRs have the capacity to activate cells.
The KIR genes are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). KIR molecules are extremely polymorphic, meaning their gene sequences differ significantly between individuals, so that different individuals have different arrays/repertoires of KIR genes.
The KIR proteins are categorized by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM). Whereas KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals.
The three Ig-domain from of inhibitory killer cell Ig-like receptor 1(KIR3DL1, NKB1, nkat3, p70KIR) is a NK cell receptor for polymorphic HLA-B determinant. KIR3DLl recognizes the Bw4 determinant defined by sequence motifs at positions 77-83 of the HLA-B heavy chain. The cytoplasmic tail of KIR, which contains two immunoreceptor tyrosine-based inhibition motifs (ITIMs), mediates inhibitory signal transduction that prevents killer cell-mediated cytotoxicity. A His-tag fusion protein of KIR3DL1 cytoplasmic tail (361-444aa) was overexpressed as insoluble protein aggregates (inclusion bodies).

L-threonine to glycine degradation consists of a two-step biochemical pathway which involvs the enzymes L-threonine dehydrogenase and 2-amino-3-ketobutyrate coenzyme A ligase. L-Threonine is initially converted into 2-amino-3-ketobutyrate by L-threonine dehydrogenase. Glycine C-Acetyltransferase (GCAT) is the 2nd enzyme in this pathway, which subsequently catalyzes the reaction between 2-amino-3-ketobutyrate and coenzyme A to form glycine and acetyl-CoA. The GCAT enzyme is regard as a class II pyridoxal-phosphate-dependent aminotransferase. GCAT is strongly expressed in the heart, brain, liver and pancreas. GCAT is also found in lung.

Chemokine (C-X-C motif) ligand 1 (CXCL1) is a small cytokine belonging to the CXC chemokine family that was previously called GRO1 oncogene, Neutrophil-activating protein 3 (NAP-3) and melanoma growth stimulating activity, alpha (MSGA-a). It is secreted by human melanoma cells, has mitogenic properties and is implicated in melanoma pathogenesis. CXCL1 is expressed by macrophages, neutrophils and epithelial cells, and has neutrophil chemoattractant activity. CXCL1 plays a role in spinal cord development by inhibiting the migration of oligodendrocyte precursors and is involved in the processes of angiogenesis, inflammation, wound healing, and tumorigenesis. This chemokine elicits its effects by signaling through the chemokine receptor CXCR2. The gene for CXCL1 is located on human chromosome 4 amongst genes for other CXC chemokines.

Ubiquinol-Cytochrome C Reductase Hinge Protein (UQCRH) is a member of the UQCRH/QCR6 family. UQCRH is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. The UQCRH protein mediates formation of the complex between cytochromes c and c1.

L-Asparaginase is an enzyme that depletes L-Asparagine "an important nutrient for cancer cells" resulting in cancer/tumor cell starvation. L-asparaginase is an anti-tumor agent derived from E.coli.,which can inhibit the growth of malignant cells. It is used mainly for the induction of remission in acute lymphoblastic leukaemia. Because of the lymph node origin of malignant B cells in Multiple Myeloma, L-Asparagine is an essential amino acid for their cell metabolism, and, consequently, L-Asparaginase may be of value in managing the disease.
The rationale behind asparaginase is that it takes advantage of the fact that ALL cellsare unable to synthesize the non-essential amino acidasparaginewhereas normal cells are able to make their own asparagine. These leukemic cells depend on circulating asparagine. Asparaginase however catalyzes the conversion of L-asparagine to aspartic acidand ammonia. This deprives the leukemic cell of circulating asparagine.

Treponema pallidum is a gram-negative spirochaete bacterium and is considered to be metabolically crippled. There are at least four known subspecies: T. pallidum pallidum, T. pallidum pertenue, T. pallidum carateum and T. pallidum endemicum. The helical structure of T. pallidum pallidum allows it to move in a corkscrew motion through viscous mediums such as mucus. Treponema pallidum sub sp. pallidum has one of the smallest bacterial genomes at 1.14 million base pairs (Mb) and has limited metabolic capabilities, reflecting its adaptation through genome reduction to the rich environment of mammalian tissue.

HMOX1 cleaves the heme ring at the alpha methene bridge to form Biliverdin. Biliverdin is then converted to Bilirubin by Biliverdin reductase. In physiological state, the highest activity of HMOX1 is found in the spleen, where senescent erythrocytes are sequestrated and destroyed. Heme Oxygenase-1 is involved in the regulation of cardiovascular function and its adaptive response to a variety of stressors. HMOX1 is induced in the colon of ulcerative colitis. HMOX1 is found to overexpress with a higher extent of intraplaque angiogenesis implies a multi-faceted role for HMOX1 in modulating the progression of atherosclerosis. HMOX1 expression reduced LPS-stimulated secretion of MCP-1, IL-6, IL-10, and TNF-alpha in murine and human macrophages.

A natural cytotoxicity receptor (NCR) NKp46 has been shown to represent a novel NK cell-specific molecule involved in human NK cell activation. The natural cytotoxicity receptors (NCRs) are a recently characterized family of Ig-like activation receptors that appear to be major triggering receptors in tumor cell recognition. The three known NCRs include NKp46 and NKp30, which are expressed on circulating NKcells, and NKp44, which is expressed only on activating NK cells. NKp46 has been implicated in NK cell-mediated lysis of several autologous tumor cells, pathogen-infected cell lines and mononuclear phagocytes infected with an intracellular bacterium. The Lysis of tumor cells by NK-cells involves recognition by NKp46 of heparan sulfate moieties of membrane heparan sulfate proteoglycans. Furthermore, NKp46 is a surface receptor involved in NK-cell cell death by apoptosis. NKp46 has two extracellular Ig-like domains followed by a ~40 residue stalk region, a type I transmembrane domain, and a short cytoplasmic tail. The extracellular Ig-like domain of NKp46 (22-255aa) is purified by FPLC gel-filtration chromatography, after refolding of the isolated inclusion bodies in a redox buffer. In addition, engagement of the antigen with the monoclonal antibody stimulates intracellular calcium levels and the synthesis of cytokines. CD59 is an NKp46 coreceptor (by physical association) together they activate cytotoxicity of human NK-cells, their engagement results in tyrosine phosphorylation of CD3-zeta chains associated with NKp46. Reduced cell surface expression of NKp46 and other NK-cell receptors is linked to the impaired NK-cell cytolytic function in viremic HIV-1 infection.

Growth-hormone-releasing hormone (GHRH), also known as growth-hormone-releasing factor (GRF or GHRF) or somatocrinin, is a 44-amino acidpeptide hormoneproduced in the arcuate nucleusof the hypothalamus.
GHRH is released from neurosecretory nerve terminals of these arcuate neurons, and is carried by the hypothalamo-hypophysial portal circulation to the anterior pituitary glandwhere it stimulates growth hormone(GH) secretion. GHRH also stimulates the production of GH. GHRH is released in a pulsatile manner, stimulating similar pulsatile release of GH. In addition, GHRH also promotes slow-wave sleepdirectly.

SAA1 protein is an acute phase apolipoprotein reactant which is produced mostly by hepatocytes and under regulation of inflammatory cytokines. SAA1 (Serum amyloid A1) protein is produced mainly in the liver and circulates in low levels in the blood. The SAA1 seems to have a role in the immune system. SAA1 protein levels increase in the blood and other tissues under conditions of inflammation. SAA1 may facilitate the repair of injured tissues; it also acts as an antibacterial agent, and signals the migration of germ-fighting cells to sites of infection. SAA1 also functions as an apolipoprotein of the HDL complex.
Elevated levels of SAA1 ultimately affect secondary amyloidosis, extracellular amassing of amyloid fibrils, resulting from a circulating precursor, in a variety of tissues and organs. The most widespread type of amyloidosis appears secondary to chronic inflammatory disease, mainly rheumatoid arthritis. The SAA1 cleavage product a designated amyloid protein A is deposited systemically as amyloid in vital organs such as the liver, spleen, and kidneys in chronic inflammatory diseases patients. These deposits are extremely insoluble and resistant to proteolysis; they disrupt tissue structure and compromise performance.

NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 (NDUFS3) is a member of the complex I 30 kDa subunit family. NDUFS3 is one of the iron-sulfur protein (IP) components of mitochondrial NADH:ubiquinone oxidoreductase (complex I). This complex is the first enzyme complex in the electron transport chain of mitochondria. The iron-sulfur protein (IP) fraction of complex I consists of seven subunits. NDUFS3 gene mutations are linked with Leigh syndrome resulting from mitochondrial complex indefficiency.

Binds to tnfrsf13b/taci and tnfrsf17/bcma. tnfsf13/april binds to the same 2 receptors, together, they form a 2 ligands -2 receptors pathway involved in the stimulation of b- and t-cell function and the regulation of humoral immunity. A third b-cell specific baff-receptor (baffr/br3) promotes the survival of mature b-cells and the b-cell response. B Lymphocyte Stimulator functions as a potent B-cell growth factor in costimulation assays. Administration of BAFF Human recombinant to mice disrupts splenic B-cell and T-cell zones and results in elevated levels of serum immunoglobulin.

RANKL binds to tnfrsf11b/opg and to tnfrsf11a/rank. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive t-cell proliferation. May be an important regulator of interactions between t-cells and dendritic cells and may play a role in the regulation of the t-cell-dependent immune response. sRANKL may also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.

Hepatitis B is one of a few known non-retroviralviruses which employ reverse transcriptionas a part of its replication process. (HIV, a completely unrelated virus, also uses reverse transcription, but it is a retrovirus.) HBV invades the cell by binding to surface receptor and become internalized. The viral core particles then migrate to the hepatocyte nucleus and the partially double-stranded, relaxed circular genomes (RC-DNA) are repaired to form a covalently closed circular DNA (cccDNA), which is the template for viral genomic and sub-genomic RNAs by cellular RNA polymerase II. Of these, the pregenomic RNA (pgRNA is selectively packaged into progeny capsids and is then reverse-transcribed into new RC-DNA. The core can either bud into the endoplasmic reticulum to be enveloped or exported from the cell or recycled back into the genome for conversion to cccDNA.

Entry of HSV into the host cell involves interactions of several viral glycoproteins with cell surface receptors. The virus particle is covered by an envelope which, when bound to specific receptors on the cell surface, will fuse with the cell membrane and create an opening, or pore, through which the virus enters the host cell. The sequential stages of HSV entry are analagous to those of other viruses. At first, complementary receptors on the virus and cell surface bring the two membranes into proximity. In an intermediate state, the two membranes begin to merge, forming a hemifusion state. Finally, a stable entry pore is formed through which the viral envelope contents are introduced to the host cell.

Chikungunya is an infection caused by the chikungunya virus which is passed to humans by two species of mosquito of the genus Aedes: A. albopictus and A. aegypti. Animal reservoirs of the virus include monkeys, birds, cattle, and rodents. The features of the disease are a sudden onset of fever 2-4 days after exposure. The fever typically lasts 2-7 days, while the associated joint pains usually last weeks or months but sometimes years. The mortality rate is a little less than 1 in 1,000. The disease has occurred in outbreaks in Asia, Europe and the Americas since 2004. CHIKV is a single-stranded positive-sense RNA genome, 11,800 nts long which encodes 2 open reading frames. The nucleocapsid is tightly enveloped by a host-derived lipid bilayer (envelope) supporting the virus-encoded envelope proteins. 80 glycoprotein spikes are C- terminally anchored within the viral envelope. The structural polyprotein is translated from a viral sub genomic mRNA, while as the 5 structural proteins (capsid, E3, E2, 6K, E1) are translated as a single polyprotein, from which capsid (C) is cleaved off to encapsidate. The envelope polyprotein precursor E3-E2-6K-E1 is translocated to the endoplasmatic reticulum. Polyprotein is processed by host signalases, resulting in E3, E2 & E1 forming viral hetero-trimeric spikes. The viral spikes majorly contains E2 and E1 facilitate cell receptor recognition, cell entry thru pH-dependent endocytosis and support viral budding.

VZV is closely related to the herpes simplex viruses(HSV), sharing much genomehomology. The known envelope glycoproteins (gB, gC, gE, gH, gI, gK, gL) correspond with those in HSV, however there is no equivalent of HSV gD. VZV virons are spherical and 150-200 nm in diameter. Their lipidenvelope encloses the nucleocapsid of 162 capsomeres arranged in a hexagonalform. Its DNAis a single, linear, double-stranded molecule, 125,000 nt long. The virus is very susceptible to disinfectants, notably sodium hypochlorite. Within the body it can be treated by a number of drugs and therapeutic agents including aciclovir, zoster-immune globulin(ZIG), and vidarabine.

SDF-1 (stromal cell-derived factor-1) is small cytokine belonging to the chemokine family that is officially designated Chemokine (C-X-C motif) ligand 12 (CXCL12). It is produced in two forms, SDF-1?/CXCL12a and SDF-1?/CXCL12b, by alternate splicing of the same gene. Chemokines are characterized by the presence of four conserved cysteines, which form two disulfide bonds. The CXCL12 proteins belong to the group of CXC chemokines, whose initial pair of cysteines are separated by one intervening amino acid. CXCL12 is strongly chemotactic for lymphocytes and has been implicated as an important cell co-ordinator during development. During embryogenesis it directs the migration of hematopoietic cells from foetal liver to bone marrow. Mice which were knocked-out for CXCL12 gene were lethal before the birth or within just 1 hour of life. As another role, CXCL12a alters also the electrophysiology of neurons. CXCL12 was shown to be expressend in many tissues in mice (including brain, thymus, heart, lung, liver, kidney, spleen and bone marrow).
The receptor for this chemokine is CXCR4, which was previously called fusin. This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 is also bound by CXCR7 receptor.
The gene for CXCL12 is located on human chromosome 10. In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.

Myxovirus Resistance 1, also known as MX1 is a guanosine triphosphate (GTP)-metabolizing protein which takes part in the cellular antiviral response. MX1 is induced by type I and type II IFN, and also antagonizes the replication process of some different RNA & DNA viruses. In addition, there is a related gene located adjacent to MX1 on chromosome 21, and there are multiple pseudogenes positioned in a cluster on chromosome 4.

Parathyroid hormone (PTH), or parathormone, is secreted by the parathyroid glands as a polypeptide containing 84 amino acids. It acts to increase the concentration of calciumin the blood, whereas calcitonin (a hormone produced by the parafollicular cells of the thyroid gland) acts to decrease calcium concentration. PTH acts to increase the concentration of calcium in the blood by acting upon parathyroid hormone receptorin three parts of the body: In the bones- It enhances the release of calcium from the large reservoir contained in the bones. Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL, which can bind to osteoclast precursors containing RANK, a receptor for RANKL. The binding of RANKL to RANK stimulates these precursors to fuse, forming new osteoclasts which ultimately enhances the resorption of bone.
In the kidney- It enhances active reabsorption of calcium from distal tubules and the thick ascending limb.
In the intestine- It enhances the absorption of calcium in the intestine by increasing the production of vitamin D and upregulating the enzyme responsible for 1-alpha hydroxylationof 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D) which effects the actual absorption of calcium (as Ca2+ ions) by the intestine via calbindin.
Recombinant Human full length PTH 1-84 has potential as an anti-osteoporotic agent, due to its properties as a bone formation stimulant, it increases bone turnover, stimulating osteoblasts and reducing both vertebral and non vertebral fractures.

H3N2 is a subtype of the influenza A virus. Its name derives from the forms of the two kinds of proteinson the surface of its coat, hemagglutinin(H) and neuraminidase(N). H3N2 exchanges genes for internal proteins with other influenza subtypes. H3N2 has tended to dominate in prevalence over H1N1, H1N2, and influenza B. H3N2 strain descended from H2N2by antigenic shift, in which genes from multiple subtypes re-assorted to form a new virus. Both the H2N2and H3N2 strains contained genesfrom avian influenzaviruses.

Hepatitis B is one of a few known non-retroviralviruses which employ reverse transcriptionas a part of its replication process. (HIV, a completely unrelated virus, also uses reverse transcription, but it is a retrovirus.) HBV invades the cell by binding to surface receptor and become internalized. The viral core particles then migrate to the hepatocyte nucleus and the partially double-stranded, relaxed circular genomes (RC-DNA) are repaired to form a covalently closed circular DNA (cccDNA), which is the template for viral genomic and sub-genomic RNAs by cellular RNA polymerase II. Of these, the pregenomic RNA (pgRNA is selectively packaged into progeny capsids and is then reverse-transcribed into new RC-DNA. The core can either bud into the endoplasmic reticulum to be enveloped or exported from the cell or recycled back into the genome for conversion to cccDNA.