Protein Function: Enzymes, Regulatory Proteins, Transport Proteins, and Storage Proteins, Exams of Chemistry

Download Protein Function: Enzymes, Regulatory Proteins, Transport Proteins, and Storage Proteins and more Exams Chemistry in PDF only on Docsity! Chemistry 501 Handout 5 Protein Function Chapter 5 Dep. of Chemistry & Biochemistry Prof. Indig Lehninger. Principles of Biochemistry. by Nelson and Cox, 5th Edition; W.H. Freeman and Company Enzymes Largest class of proteins. More than 3000 enzymes known. Enzymes are biological catalysts that accelerate reactions. Enzymes are generally highly specific and react with only one substrate to form one product and can enhance reaction rates by as much as 1016. Regulatory Proteins Regulatory proteins influence the behavior or abundance of enzymes either directly or indirectly. Some bind to enzymes to modulate their activity, others bind to DNA to control the level of production of an enzyme. Transport Proteins Transport proteins deliver specific substances (e.g. Hemoglobin). Storage Proteins These proteins act as a biological reservoir for specific nutrients. The classic example is ferritin that binds and stores iron in mammals and plants. Contractile Proteins actin and myosin in muscles of animals tubulin in bacterial cilia Structural proteins provide strength to cells keratins –hair horns and fingernails collagen –connective tissue, elastin - elasticity The amino acid sequences of whale myoglobin and the α and β chains of human hemoglobin * E (glutamate) replaced by V (valine) in Sickle anemia * Protein-ligand interactions can be described quantitatively P + L ↔PL ka = [PL] [P][L] = associationconstant ka [L] = [PL] [P] θ = bindingsitesoccupied totalbindingsites = [PL] [PL]+ [P] θ = ka [L][P] ka [L][P]+ [P] = ka [L] ka [L]+1 = [L] [L]+ 1 ka or kd = [P][L] [PL] = dissociationconstant [PL] = [P][L] kd θ = [L] [L]+ kd Graphical representation of ligand binding Hemoglobin undergoes a structural change on binding oxygen Changes in conformation near heme on O2 binding to deoxyhemoglobin Some ion pairs that stabilize the T state of deoxyhemoglobin Hemoglobin binds oxygen cooperatively Tense Relaxed Hemoglobin also transports H+ and CO2 (to kidneys and lungs) CO2 + H2O = H + + HCO3 - Reaction catalyzed by carbonic anhydrase (particularly abundant in erytrocytes) Effect of pH on the binding of oxygen to hemoglobin The effect of pH and CO2 concentration on the binding of oxygen by hemoglobin is called the Bohr effect Hb + O2 = HbO2 HHb+ + O2 = HbO2 + H + Protonated form of hemoglobin end of each globin chain tissues blood lungs Oxygen binding to hemoglobin is regulated by 2,3-bisphosphoglycerate HbBPG + O2 = HbO2 + BPG Effect of BPG on the binding of oxygen to hemoglobin Binding of BPG to deoxyhemoglobin (example of heterotropic allosteric modulation) S state T state Sickle-cell anemia is a molecular disease of hemoglobin Normal erythrocytes Variably shaped erythrocytes (spiny + sickle-shaped) Subtle differences in conformation result from a single residue change in the β chains As a result HbS has hybrophobic patches on its surface, what causes the molecules to aggregate into strands that align into insoluble fibers Antibodies have two identical antigen-binding sites Structure of immunoglobulin G (IgG) Ribbon model of the first complete IgG molecule to be crystalized and structurally analyzed (PDB ID 1IGT) Binding of IgG to an antigen Phagocytosis of an antibody-bound virus by a macrophage IgM pentamer of immunoglobulin units Polypeptide of Mr 20,000 found in both IgA and IgM Antibodies bind tightly and specifically to antigen Induced fit in the binding of an antigen to IgG Polyclonal antibodies: produced by many different B lymphocytes responding to one antigen, such as a protein injected into an animal (bind specific, different epitopes within the antigen). Monoclonal antibodies: produced by a population of identical B cells (a clone) grown in cell culture (homogeneous, all recognize the same epitope). The major proteins of muscle are myosin and actin Myosin Representation of the S1 fragment left-handed Coiled coil large globular domain (site for ATP hydrolysis) Protein interactions modulated by chemical energy: Actin, Myosin, and molecular motors The major components of muscle In muscle cells molecules of myosin aggregate (structures called thick filaments) Thin filament: filamentous assemblage of G-actin monomers that polymerize two by two giving the appearance of two filaments spiraling about one another (right-handed) Structure of skeletal muscle relaxed muscle contracted muscle Thin filaments Thick filaments Thin structure perpendicular to the thin filaments and serving as anchor to which the thin filaments are attached Regulation of muscle contraction by tropomyosin and troponin. Tropomyosin Troponin C Troponin T DY SFP VY == KT Sick SOS MCRI Molecular Motors Group http://mc11.mcri.ac.uk/mpubs/mpubs2006.html Cross R.A. PNAS 103, 8911-8912, 2006 Nonpolar, aliphatic R groups coo" coo" coo™ coo- + + | LH + | H3N—C—H =-H3N—C—H i H3;N—C—H | | HON CH2 | CH; Ab H.C CHa city ‘CHs Glycine Alanine Proline Valine coo- coo" coo- + + | + HAN —5-H HN—C—H H3;N—C—H Ci cma cts cH Ae i i CH3 ~CH3 cH; : CH Leucine Isoleucine = Methionine Aromatic R groups coo coo coo™ * «1 , H;N—C—H H;N—C—H HN—¢ —H CH, | | cH, cH, ¢=CH x O QO NH OH Phenylalanine Tyrosine Tryptophan Polar, uncharged R groups coo" coo" coo" H3;N—C—H H;N—C—H H,N—C—H CH,OH H—C—OH CHa CH3 hy Serine Threonine Cysteine Arginine Histidine coo- coo Wi—C—H w—c—H He oa ¢ CHa aN Hn’ So i 7X Hn’ Yo Asparagine Glutamine Negatively charged R groups coo- coo- + | + | H-t-H H3;N—C—H CH, a coo- CH, coo™ Aspartate Glutamate