Download Some funcaon of proteins

pensum Some func9on of proteins Enzymes (luciferase) Transport (hemoglobin) Structure (kera9n) pensum General structure of an amino acid This structure is common to all but one of the α-­‐amino acids. (Proline, a cyclic amino acid, is the excep9on.) The R group, or side chain (red), aOached to the α carbon (blue) is different in each amino acid. pensum Amino acids: protein building blocks •  20 covalently linked amino acids form all proteins •  Make up widely diverse protein products such as enzymes, hormones, an9bodies, transporters, muscle fibers, feathers, spider webs, rhinoceros horns, milk proteins, an9bio9cs, mushroom poisons etc. •  9 amino acids essen9al for humans (needs to be added via food/drinks, all 20 needed for protein synthesis) pensum Geometry of carbon bonding Carbon atoms have a characteris9c tetrahedral arrangement of their four single bonds. pensum Stereoisomerism in amino acids pensum Stereoisomerism and amino acids •  Only L-­‐enan9omers of amino acids are found in proteins •  D-­‐amino acids exist in nature, and some play important biochemical roles such as intermediates in amino acid metabolism and in polypep9des in some bacterial walls, neurotransmiOer •  Recently, proteins are synthesized only of D-­‐amino acids. These are then mirror images of proteins synthesized by L-­‐amino acids and have ac9vity towards D-­‐amino acids/proteins. Hence, “D-­‐life” would be possible. pensum The R-­‐groups, overview •  Nonpolar, alipha9c R groups –  E.g. glycine: •  Aroma9c R groups –  E.g. phenylalanine: •  Polar, uncharged R groups –  E.g. serine: •  Posi9vely charged R groups –  E.g. lysine: •  Nega9vely charged R groups –  E.g. Aspartate: pensum Protein primary structure: Forma9on of a pep9de bond by condensa9on. pensum Pep9des are named beginning with the amino-­‐terminal residue, which by conven9on is placed at the le@. Example: The pentapep9de serylglycyltyrosylalanylleucine, Ser–
Gly–Tyr–Ala–Leu, or SGYAL. The pep9de bonds are shaded in yellow; the R groups are in red. pensum The planar pep9de group Each pep9de bond has some double-­‐bond character due to resonance and cannot rotate. The carbonyl oxygen has a par9al nega9ve charge and the amide nitrogen a par9al posi9ve change, se_ng up a small electric dipole. Virtually all pep9de bonds in proteins occur in this trans configura9on. pensum Levels of structure in proteins pensum Levels of structure in proteins •  primary structure consists of a sequence of amino acids linked together by pep9de bonds and includes any disulfide bonds. •  The resul9ng polypep9de can be arranged into units of secondary structure, such as an α helix. •  The helix is a part of the ter0ary structure of the folded polypep9de •  The ter9ary structure is itself one of the subunits that make up the quaternary structure of some mul9subunit protein, (e.g. hemoglobin). pensum Protein secondary structure (The local spa9al arrangement of the main-­‐chain atoms in a selected segment of a polypep9de chain) •  α Helix –  Right-­‐handed –  Lec-­‐handed •  β Conforma9on –  Parallell –  An9-­‐parallell •  β Turn –  1/3 of amino acid residues in β turns or loops where the polypep9de chain reverses direc9on in globular proteins having compact folded structure pensum Protein – ter9ary structure •  Every protein has a three-­‐dimensional (3D) structure that reflects its func9on •  Protein structure is stabilized by mul9ple weak interac9ons: –  Hydrofobic interac9ons are the major contributors to stabilizing the globular form of most soluble proteins (hydrofobic groups in the center of the protein, hydrophilic groups at the surface) –  Hydrogen bonds and ionic interac9ons are op9mized in the thermodynamically most stable structures •  The nature of the covalent bonds in the polypep9de backbone (rigid planar confirma9on) places natural constraints on structure by mul9ple weak interac9ons resul9ng in defined secondary structures. pensum Lysozyme structure-­‐func9on Lysozyme bind pep9doglycans (found in the cell walls of bacteria, especially Gram-­‐posi9ve bacteria), 6 sugars, and hydrolyze the glycosidic bond that connects N-­‐acetylmuramic acid with the fourth carbon atom of N-­‐acetylglucosamine. Substrate-­‐enzyme interac9on can be highly specific (lock-­‐and-­‐key, hand-­‐in-­‐glove) pensum pensum Substrate specificity – glucose oxidase (GOD) Only substrate is β-­‐D-­‐glucose (not ac9ve on α-­‐D-­‐glucose) GOD pensum Glucose oxidase Only substrate is β-­‐D-­‐glucose (not ac9ve on α-­‐D-­‐glucose) pensum pensum Enzymes act through reduc9on in ac9va9on energy pensum Possible causes of reduced ac9va9on energy •  Following ac9ve interacton and an intermediate state, enzyme and substrate fit perfectly. The enzymes bind not to the original configura9on, but to the intermediate state of the substrate in their ac9ve site (“induced fit”) •  Highly reac9ve func9onal groups concentrated in a very small space and arranged in a way that are in direct contact with the bonds of the substrate they are going to modify, thus ensuring constant exposure. The ac9ve site contains mainly nonpolar groups, which makes it resemble a nonpolar organic solvent. Organic reac9ons are generally speeded up in a nonpolar organic solvent, compared to the reac9on in polar water. In the organic environment of the ac9ve site, the few exis9ng charged polar side groups of amino acids become super-­‐reac9ve in comparison to their behavior in a watery solu9on. pensum Enzymes: biologically catalysts •  Nearly all chemical reac9ons within living cells are catalyzed by enzymes •  Enzymes speed up chemical reac9ons (due to reduc9on in ac9va9on energy) by a factor of up to 1012 •  Are not used up in reac9ons and can thus be re-­‐
used •  Substrate is converted to product in ac9ve site of enzyme •  Substrate specificity vary, can be highly specific pensum Cofactors •  Inorganic molecules (such as Fe3+, Mg2+, Mn2+ or Zn2+) •  Coenzymes: –  Organic compounds binding to ac9ve site, or close to ac9ve site. –  Modify structure of substrate or move electrons, protons or chemical groups between substrate and enzyme –  Are used up in the reac9on (and dissociate from the enzyme) –  Many derived from vitamins, example: NAD+ (vitamin B deficiency leading to pellagra)