Unformatted text preview: Lecture Set #4 -helix
A segment of a protein’s helix can cross the lipid bilayer of membrane (a protein can have more than one helix that crosses crosses the membrane). About 20 amino acids are required to span a membrane in an helix. helix. -sheets Core of most globular
proteins is made of sheets A rigid structure held together by H-bonds H ex: silk Distant parts of the
protein can fold so they rest next to each other
ECB3 4-12 ECB2 4-17 Tertiary structure This level of structure describes the Tertiary Protein Structure The folded protein is the tertiary level of structure. Many proteins are contain multiple secondary structures. completely folded protein. Contains functioning regions (domains) Most proteins are globular Has within it -helices and -sheets Has within it helices and Plus the other segments of the amino acid
chain Remember: Remember: It’s the primary sequence which determines the folding of the secondary and tertiary structures. If the 1’ structure is changed, the functional regions on the protein may also change. Note how the folded globular protein contains -helices and -sheets. Cooper 2.20 Tertiary Protein Structure
An example of protein tertiary structure is myoglobin. Myoblogin is 153 amino amino acids long; involved in oxygen transport; folded around a heme group. Quaternary Structure
A protein can have a fourth level of structure, when multiple polypeptides (subunits) come together and form the final final functional protein. Bonds (non-covalent (nonand covalent) hold the subunits together Cooper 2.18 Cooper 2.21 Bio 106 Fall 2009 Professor Owen 1 Lecture Set #4 Protein Structure What if the protein sequence is changed?? ex: sickle cell anemia —affects the
protein hemoglobin 1 amino acid change in 1º structure amino (valine (valine for a glutamate) leads to a very different 3D structure under low oxygen levels http://www.pbs.org/wgbh/evolution/library/01/2/l_012_02.html http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.section.98
(NIH) http://www.nhlbi.nih.gov/health/dci /Diseases/Sca/SCA_WhatIs.html Review: How many levels of protein structure have we examined?
A. B. C. D. E. Review … DNA translated into a sequence of amino acids (primary
structure) 20 amino acids in proteins linked by peptide bond R-group chemistry: hydrophobic/hydrophophilic Amino acid chain twists into -helices and -sheets (2nd structure) rotation around rotation around -carbon R-groups stick out Whole protein folds, often forming binding sites = domains (3rd level) More than one polypeptide can bind together to make a functional protein example: hemoglobin can have additional non-protein groups (prosthetic) nonChanges in a.a. sequence or structures can change protein 1 2 3 4 5 Structure-Based Drug Design
Cyclooxygenase Cyclooxygenase 2 enzyme acts at the site of inflamation But … NSAID = non-steroidal anti-inflammatory drugs nonantiFirst COX-2 drugs = Celebrex and Vioxx COXCelebrex Vioxx Bio 106 Fall 2009 Professor Owen 2 Lecture Set #4 Protein Structure: Disulfide Bonds A stabilizing
covalent bond Protein Function
Many proteins function as enzymes, requiring a highly selective binding of the substrate (ligand) to a particular region on the protein. Amino acid cysteine
has a sulfhydral group (-SH) and will (form covalent bonds between some between some cysteinescysteines-cysteines See Cooper Website animation 3.2 http://www.sinauer.com/cooper/4e/animations0302.html
ECB2 4-29 ECB2 4-30 Disulfide bonds do not form in proteins synthesized in the cytoplasm, only in proteins synthesized in the ER
Cooper 3.2 In an enzyme-catalyzed reaction, is the enzyme used up during the process?
A. B. C. D. E. Activation Energy of an Enzyme Yes No Maybe It depends Absolutely
ECB3 3-12 Protein Function
An enzyme functions as a catalyst – it facilitates the reaction, then the product is released, allowing the enzyme to bind another substrate molecule. Protein Function Enzymes function as catalysts speeds up reactions by reducing the activation energy for a chemical change Binding reaction:
binding catalysis release E S ES EP E P ECB3 3-15 Bio 106 Fall 2009 Professor Owen 3 Lecture Set #4 Enzyme Kinetics
The rate of an enzyme reaction (V) increases as the substrate concentration increases until a maximum value (Vmax) is (Vmax) reached.
ECB3 3-24 Michaelis-Menton Equation
Equation that gives the rate of a reaction Km = measure of the fit of the enzyme binding to its substrate (s)
(Km (Km is also called the Michaelis-Menton constant) Michaelis- Vmax = maximum velocity of the reaction The concentration of substrate at which the reaction rate is ½ the maximum (the Km) is a measure of the fit of the enzyme to its substrate. V max[ s] vo Km [ s] Enzyme Kinetics Enzyme Kinetics ECB3 3-26
Lodish 3-26 MichaelisMichaelis-Menton analysis gives numbers for comparison. Here, one can compare the binding of different substrates to an enzyme by determining its Km. Experimentally, the velocities of a reaction are plotted against the substrate concentrations. A mathematical transformation to the form of a straight line makes it easier to determine the Km and Vmax values of an enzyme. Bio 106 Fall 2009 Professor Owen 4 ...
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