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FKBP1B
Peptidyl-prolyl cis-trans isomerase FKBP1B is an enzyme that in humans is encoded by the ''FKBP1B'' gene. Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 (tacrolimus) and rapamycin (sirolimus). It is highly similar to the FK506-binding protein 1A. Its physiological role is thought to be in excitation-contraction coupling in cardiac muscle. There are two alternatively spliced transcript variants of this gene encoding different isoforms. Clinical significance Defective interaction between FKB1B and the ryanodine receptor is thought to be a potential mechanism underlying the arrhythmias seen in those with the genetic condition catecholaminergic polymorphic ventricular tachycardia Catecholaminergic polymorphic ventricular tachycardia ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecules known as product (chemistry), products. Almost all metabolism, metabolic processes in the cell (biology), cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme, pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts include Ribozyme, catalytic RNA molecules, also called ribozymes. They are sometimes descr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and non-coding genes. During gene expression (the synthesis of Gene product, RNA or protein from a gene), DNA is first transcription (biology), copied into RNA. RNA can be non-coding RNA, directly functional or be the intermediate protein biosynthesis, template for the synthesis of a protein. The transmission of genes to an organism's offspring, is the basis of the inheritance of phenotypic traits from one generation to the next. These genes make up different DNA sequences, together called a genotype, that is specific to every given individual, within the gene pool of the population (biology), population of a given species. The genotype, along with environmental and developmental factors, ultimately determines the phenotype ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immunophilin
In molecular biology, immunophilins are endogenous cytosolic peptidyl-prolyl isomerases (PPI) that catalyze the interconversion between the cis and trans isomers of peptide bonds containing the amino acid proline (Pro). They are chaperone molecules that generally assist in the proper folding of diverse "client" proteins. Immunophilins are traditionally classified into two families that differ in sequence and biochemical characteristics. These two families are: "cyclosporin-binding cyclophilins (CyPs)" and "FK506-binding proteins (FKBPs)". In 2005, a group of dual-family immunophilins (DFI) has been discovered, mostly in unicellular organisms; these DFIs are natural chimera of CyP and FKBPs, fused in either order (CyP-FKBP or FKBP-CyP). Immunophilins act as receptors for immunosuppressive drugs such as sirolimus (rapamycin), cyclosporin (such as CsA) and tacrolimus (FK506), which inhibit the prolyl isomerase activity of the immunophilins. The drug-immunophilin complexes (CsA-Cy ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cis-trans Prolyl Isomerase
Prolyl isomerase (also known as peptidylprolyl isomerase or PPIase) is an enzyme () found in both prokaryotes and eukaryotes that interconverts the ''cis'' and ''trans'' isomers of peptide bonds with the amino acid proline. Proline has an unusually conformationally restrained peptide bond due to its cyclic structure with its side chain bonded to its secondary amine nitrogen. Most amino acids have a strong energetic preference for the ''trans'' peptide bond conformation due to steric hindrance, but proline's unusual structure stabilizes the ''cis'' form so that both isomers are populated under biologically relevant conditions. Proteins with prolyl isomerase activity include cyclophilin, FKBPs, and parvulin, although larger proteins can also contain prolyl isomerase domains. Protein folding Proline is unique among the natural amino acids in having a relatively small difference in free energy between the ''cis'' configuration of its peptide bond and the more common ''trans'' fo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tacrolimus
Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After Allotransplantation, allogenic organ transplant, the risk of organ Transplant rejection, rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also be sold as a topical medication in the treatment of T cell-mediated diseases such as atopic dermatitis, eczema and psoriasis. For example, it is prescribed for severe refractory uveitis after a bone marrow transplant, exacerbations of minimal change disease, Kimura's disease, and vitiligo. It can be used to treat Dry eye syndrome#Other, dry eye syndrome in cats and dogs. Tacrolimus inhibits calcineurin, which is involved in the production of interleukin-2, a molecule that promotes the development and cell proliferation, proliferation of T cells, as part of the body's learned (or adaptive immune response, adaptive) immune response. Chemically, it is a macrolide lactone that was first discovered in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sirolimus
Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosis, and treat perivascular epithelioid cell tumour (PEComa). It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It is a mammalian target of rapamycin (mTOR) kinase inhibitor that reduces the sensitivity of T cells and B cells to interleukin-2 (IL-2), inhibiting their activity. This compound also has a use in cardiovascular drug-eluting stent technologies to inhibit restenosis. It is produced by the bacterium '' Streptomyces hygroscopicus'' and was isolated for the first time in 1972, from samples of ''Streptomyces hygroscopicus'' found on Easter Island. The compound was originally named rapamycin after the native name of the island, Rapa Nui. Sirolimus was initially deve ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FKBP1A
Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the ''FKBP1A'' gene. It is also commonly referred to as FKBP-12 or FKBP12 and is a member of a family of FK506-binding proteins ( FKBPs). Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 (tacrolimus) and rapamycin (sirolimus). It interacts with several intracellular signal transduction proteins including type I TGF-beta receptor. It also interacts with multiple intracellular calcium release channels including the tetrameric skeletal muscle ryanodine receptor. In mouse, deletion of this homologous gene causes congenital heart disorder known as noncompaction of left ventricular myocardium. Multiple alternatively spliced variants, encoding the same protein, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Muscle Contraction
Muscle contraction is the activation of Tension (physics), tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such as when holding something heavy in the same position. The termination of muscle contraction is followed by muscle relaxation, which is a return of the muscle fibers to their low tension-generating state. For the contractions to happen, the muscle cells must rely on the change in action of two types of Myofilament, filaments: thin and thick filaments. The major constituent of thin filaments is a chain formed by helical coiling of two strands of actin, and thick filaments dominantly consist of chains of the Motor protein, motor-protein myosin. Together, these two filaments form myofibrils - the basic functional organelles in the skeletal muscle system. In vertebrates, Muscle cell#Muscle contraction in striated muscle, skele ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cardiac Muscle
Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of the heart. The cardiac muscle (myocardium) forms a thick middle layer between the outer layer of the heart wall (the pericardium) and the inner layer (the endocardium), with blood supplied via the coronary circulation. It is composed of individual cardiac muscle cells joined by intercalated discs, and encased by collagen fibers and other substances that form the extracellular matrix. Cardiac muscle contracts in a similar manner to skeletal muscle, although with some important differences. Electrical stimulation in the form of a cardiac action potential triggers the release of calcium from the cell's internal calcium store, the sarcoplasmic reticulum. The rise in calcium causes the cell's myofilaments to slide past each other i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ryanodine Receptor
Ryanodine receptors (RyR) make up a class of high-conductance, intracellular calcium channels present in various forms, such as animal muscles and neurons. There are three major isoforms of the ryanodine receptor, which are found in different tissues and participate in various signaling pathways involving calcium release from intracellular organelles. Structure Ryanodine receptors are multidomain homotetramers which regulate intracellular calcium ion release from the sarcoplasmic and endoplasmic reticula. They are the largest known ion channels, with weights exceeding 2 megadaltons, and their structural complexity enables a wide variety of allosteric regulation mechanisms. RyR1 cryo-EM structure revealed a large cytosolic assembly built on an extended Alpha solenoid, α-solenoid scaffold connecting key regulatory domains to the pore. The RyR1 pore architecture shares the general structure of the six-transmembrane ion channel superfamily. A unique domain inserted between the secon ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Heart Arrhythmia
Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – above 100 beats per minute in adults – is called tachycardia, and a resting heart rate that is too slow – below 60 beats per minute – is called bradycardia. Some types of arrhythmias have no symptoms. Symptoms, when present, may include palpitations or feeling a pause between heartbeats. In more serious cases, there may be presyncope, lightheadedness, Syncope (medicine), passing out, shortness of breath, chest pain, or decreased level of consciousness. While most cases of arrhythmia are not serious, some predispose a person to complications such as stroke or heart failure. Others may result in cardiac arrest, sudden death. Arrhythmias are often categorized into four groups: premature heart beat, extra beats, supraventricular tachycard ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Catecholaminergic Polymorphic Ventricular Tachycardia
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited genetic disorder that predisposes those affected to potentially life-threatening abnormal heart rhythms or arrhythmias. The arrhythmias seen in CPVT typically occur during exercise or at times of emotional stress, and classically take the form of bidirectional ventricular tachycardia or ventricular fibrillation. Those affected may be asymptomatic, but they may also experience blackouts or even sudden cardiac death. CPVT is caused by genetic mutations affecting proteins that regulate the concentrations of calcium within cardiac muscle cells. The most commonly identified gene is RYR2, which encodes a protein included in an ion channel known as the ryanodine receptor; this channel releases calcium from a cell's internal calcium store, the sarcoplasmic reticulum, during every heartbeat. CPVT is often diagnosed from an ECG recorded during an exercise tolerance test, but it may also be diagnosed with a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
