Interpretation:
How the study of LDL receptor binding by a human rhinovirus HRV2, provided support for model of LDL particle displacement should be discussed.
Concept Introduction:
LDL receptor has five domains. N terminal LDL binding domain contains seven cysteine rich repeats referred as R1 to R7. Next epidermal growth factor repeats and ß propeller module can be found. Those segments are followed by O-linked oligosaccharide, a membrane spanning segment and another segment extended towards the cytosol. LDL particles bind with R4 and R5 cysteine repeats. At low pH, the LDL receptor polypeptide folds so that ß propeller domain is associated with R4 and R5 displacing the LDL particle. These two repeats contain two loops connected by 3 disulfide bonds. Second loop of each repeat have Asp and Glu acidic residues and acts as a Ca2+ binding site.
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Chapter 24 Solutions
Biochemistry
- Antibiotics that target bacterial molecules not previously exploited are desperately needed. One such target is the protein FtsZ. The small molecule 3-methoxybenzamide (3-MBA) is known to inhibit FtsZ in Bacillus subtilis but is not bacteriocidal. Nonetheless, researchers reasoned that 3-MBA offered a good starting point for the synthesis of a molecule that might be a potential drug candidate. Over 500 3-MBA analogues were synthesized and screened; one called PA190723 was extremely potent in its capacity to bind FtsZ and inhibit bacterial growth. In fact, when used in a mouse model, PA190723 was bacteriocidal against methicillinand multidrug-resistant Staphylococcus aureus. What makes FtsZ a good drug target? What preliminary information about 3-MBA would be helpful if you were designing the 3-MBA analogues? As these researchers move forward with clinical (human) testing, what other parameters and outcomes must be assessed besides the bacteriocidal activity of PA190723?arrow_forwardSmall molecules are used as inhibitors of protein action - as drugs. They most often do this by blocking the active site within the protein. Potential drugs can be screened computationally to determine if they are strongly bound to the protein. Figure 1 shows a possible conformation of a candidate drug molecule, 4-bromo-2- carboxymethylamide-pyrrole (abbreviation: BCMAP) at the active site of a protein (abbreviation: PR). Figure 2 shows the full protein structure whilst figure 3 shows a known inhibitor of the protein at the site, overlayed with another calculated conformer of BCMAP. (a) Explain what types of interactions, both intermolecular and intramolecular, that a molecular mechanics forcefield must be able to describe in order to be able to accurately determine the geometry of BCMAP in the protein. Identify which interactions will be the most important to describe accurately. Figure 1.4-bromo-2-carboxymethylamide-pyrrole (BCMAP) (C, N, O, and Br atoms in yellow, blue, red, and…arrow_forwardPart A Shown above is a schematic diagram of the E. coli leader peptidase (Lep) which has several basic amino acids in a cytoplasmic loop. Propose a mutant of Lep that would be a test of the "inside positive" rule for the orientation of proteins in membranes. Match the words in the left column to the appropriate blanks in the sentences on the right. Make certain each sentence is complete before submitting your answer. terminal reversed same (+) (-) center 1. Make mutant Lep that substitutes noncharged residues for the chains in the loop, and put charged side chains in 2. If the inside-positive rule applies, the mutant ought to have the membrane. Reset Help charged side positions. orientation in thearrow_forward
- A laboratory in Japan performed a similar experiment on earthworms from different localities of the Japanese archipelago, but instead of linking trypsin activity within worms to anatomical features, they were interested in geographical differences in the ability of the worms to breakdown environmental pollutants using the enzyme polyphenol oxidase. The protocol was similar to the one you used, except that enzyme activity was measured from 100 µl of worm extract. Data obtained are displayed below: Locality Replicate Amount of product Concentration of total protein in worm extract (µg/ml) liberated over 10 minutes (pmol) Hokkaido 1 101 4 87 3 3 107 4 4 88 3 5 89 Hon-shu 1 126 2 2 120 3 3 156 4 4 153 5 5 119 4 Куu-shu 1 103 4 2 99 5 3 94 4 108 3 5 110 5 Okinawa 1 88 3 2 90 4 3 96 4 100 112 5 5 3 From the data in the table, calculate the specific activity of polyphenol oxidase (in units of umol/min/mg protein) from each locality, presenting the data as mean + standard error (n=5).arrow_forwardIn each case, these are enzymes that catalyze thesame reaction in different species. The question is: are they related or not? i.e. Are the structures essentially the same? Often you can get similar reactions from proteins thatevolved from a common ancestor (e.g., trypsin and chymotrypsin). Sometimes the samereaction can be catalyzed by proteins with very different evolutionary origins and with verydifferent structures (e.g., trypsin and subtilisin). Your job is to decide if these proteins have fundamentally different folds or if they have basically the same fold. Briefly justify your answer.1. Aminopeptidases from a mammal (PR1A) and the malaria parasite (PR1B)2. Bisphosphoglycerate mutase from a mammal (PR2A) and the toxoplasma parasite(PR2B)arrow_forwardWe humans do not express an alpha-Galactosidase enzyme and therefore cannot break down stachyose but the bacteria that live in our large intestine can. These bacteria contain an alpha-Galactosidase enzyme that hydrolyzes the galactopyranosyl-alpha (1-6) glycosidic bonds. The bacteria then ferment the products to generate the gas that is famously associated with eating beans. Draw the Haworth projections of the products of alpha-Galactosidase catalyzed reaction. Name the products of this enzyme catalyzed reaction.arrow_forward
- Example 14.6 The oxygen requirement for cell growth in glueose can be represented by the following equation (Mateles, 1971) 32NC+8(Nh2)+16(No2) Fx/sM +yo2 – 2.67yc + 1.714YN2 – 8y H2 ro2 = In which ro2 is the oxygen required for each gram of cells produced, N stands for no. of atoms present in each molecule substrate, y stands for mass fractions and M is the MW of the substrate. The yeast cell may be considered to be CH1.800.5NO.2. Calculate rO2 if the yield factor (Yx/s) is 0.46g of cells produced for each gram of substrate consumed.arrow_forwardLysozyme is an enzyme that hydrolyzes bacterial cell wall polysaccharides. When this reaction is carried out in the presence of H218O, it is observed that there is retention of configuration at the C1 carbon of the D site sugar as shown below Two key amino acid side chains (an Asp and a Glu) essential for lysozyme’s catalytic activity are positioned above and below the C1-O bond that is cleaved as shown below. Suggest a plausible mechanism for the reaction that starts with a nucleophilic attack at C1.arrow_forwardYou are studying the uptake of L-leucine by epithelial cells of the mouse intestine. Measurements of the rates of uptake of L-leucine and severalof its analogs, with and without Na+ in the assay buffer, yield the results given in the table below. What can you conclude about the properties and mechanism of the leucine transporter? Would you expect L-leucine uptake to be inhibited by ouabain?arrow_forward
- Sydney Brennen isolated Salmonella typhimurium mutants that were implicated in the biosynthesis of tryptophan and would not grow on minimal medium supplemented with intermediates in tryptophan biosynthesis, some mutants were able to grow while others remained unable to grow. Review the data attached to order the biosynthetic pathway by both enzymatic step and by intermediate biomolecule. Label the step impacted by each of the mutant cell lines.arrow_forwardQuestion:- Part A) How does the molecular mechanism of elongation arrest by SRP differ between Bacillus and Mammalian systems? Please list all the differences and why. Thank you and please explain. Part B) List four interactions of the Ffh M domain in SRP mechanism.arrow_forwardPredict the location(s) (intracellular or extracelular) and a brief description of WHY based on your knowledge of the transport processes in the following constructs. Assume a start codon is present and include any proteolytic processing that would be likely. 1. A PTS1 C-term peroxisomal targeting seq added to C term of a normally secreted protein with usual N -terminal signal sequence 2. Adding of N-terminal mitochondrial targeting sequence to protein with internal nuclear localization seq. 3. Adding N-terminal signal sequence of secreted protein to N-terminus a mitochondria matrix protein precursor with mitochondrial targeting sequence still presentarrow_forward
- BiochemistryBiochemistryISBN:9781305577206Author:Reginald H. Garrett, Charles M. GrishamPublisher:Cengage LearningBiology: The Dynamic Science (MindTap Course List)BiologyISBN:9781305389892Author:Peter J. Russell, Paul E. Hertz, Beverly McMillanPublisher:Cengage Learning