The sequence CAD is a little larger than half of a loop of the peptide backbone helix. Since the β 1-adrenergic binding across ACADL is selectively binding also across CAD, it is an assumption that the binding site requires one full loop of an α-helix. The mechanism by which one small molecule agonists on associating with only one of the loops in only one of the α-helices would increase the amplitude of signaling for the entire macromolecular transmembrane domain of receptor is not at all self-evident. Although macromolecular processes such as shielding and hydrophobicity affect membrane potential, ion channels enable cross membrane signaling and intracellular communication. The ion channel portion of the receptor is composed of seven α-helical backbone peptides, each perpendicular to the lipid membrane: adjacent helices align anti-parallel, except the first and the last of the seven helices instead align parallel. Changing only one receptor amino acid markedly alters agonist activity. Within one loop of one α-helix within the transmembrane region, the β 1-adrenergic agonists fit better to the sequence ACADL and β 1-agonists fit better to ASADL. The size and molecular weight of these agonists is 0.5% of the size and weight of the receptor. Binding site specificity for β 2-adrenergic agonists results in stimulation of respiratory functions to treat acute bronchitis versus β 1-adrenergic agonists stimulation of cardiac output. The crystallographic structure of the β 2-adrenergic receptor has 56,000 atoms, about a third of which are transmembrane a-helical backbone peptides. from agonist binding) can/will alter the shape of an α-helix. Only external forces which specifically affect circumference, pitch and/or phase (e.g. Wavefront Topology System and Finite Element Methods calculate this specific helical shape based only upon circumference, pitch, and phase. More precisely, eleven atoms in peptide backbone routinely equal one loop of a helix, instead of eleven amino acid residues equaling three loops of a helix therefore, an α-helix can begin (or end) at any specific atom in a peptide backbone, not just at any specific amino acid. Consequently, atomic coordinates in a peptide backbone α-helix match the data points of individual atom (and atom types) in the backbone. A model of an α-helix is presented in which of pitch occurs at angles both smaller and larger than 180˚ n. The understanding of the mechanism by which a small molecule on binding to a site on one single loop of a helix produces a specific agonist activity on an entire transmembrane ion channel is uncertain. The α-agonist responsible for this selective reaction is only 0.5% of the receptor molecular weight, and only 1.5% of the weight of the transmembrane portion of the receptor. Within one of the seven transmembrane ion channel helices in the β 2-receptor, one loop of a helix ACADL has previously been proposed as the site that explains β 2activity (fights acute bronchitis) whereas ASADL in the β 1-receptor at the correspondding site explains β 1-activity (cardiac stimulation). The 3-D structure of the β-adrenergic receptor with a molecular weight of 55,000 daltons is available from crystallographic data. Keywords: Helix Alpha-Helix Circumference Pitch, phase peptide backbone Wavefront Topology System Finite Element Method Received 12 July 2012 revised 23 August 2012 accepted 29 August 2012 1Agricultural Research Service, USA Department of Agriculture, Beltsville, USA *Corresponding Author: of Engineering, Morgan State University, Baltimore, USA
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |