Binding Pocket exam questions
Fall 2016 Exam 1 (closed book, this question was originally used in Fall 2008 as an open book)
13. Chiaro and coworkers have found that leukotriene metabolites are unexpectedly binding to the aryl hydrocarbon receptor protein (see Biochemistry 2008, 47, 8445). Examine the structure of the 5,6 leukotriene A4 metabolite shown below. In the spaces labeled A, B, and C, suggest an example of amino acids that would be used in those positions by a protein that binds 5,6 leukotriene A4. Briefly explain your reasoning. (9 pts.)
Fa2015 Exam 1 (closed book)
11. The structure of resveratrol is shown in the binding pocket presented below. Tu, L.-H. and coworkers have examined the ability of resveratrol to bind to islet amyloid polypeptide as part of a larger effort to cure Alzheimer’s Disease (see Biochemistry 2015, 54, 666-76 DOI: 10.1021/bi501016r). (10 pts.)
a) Tu and coworkers report that a phenylalanine in position 15 is important for the binding of resveratrol to islet amyloid polypeptide. Would you expect Phe15 to be found at position A, B, or C of the cartoon-binding site? Briefly explain your reasoning.
b) Tu and coworkers also reported that His18 was important for binding. Is His-18 a potential candidate for position A, position C or either position in the cartoon diagram? Briefly explain your reasoning.
Final Exam 2016, 2014, 2010 (closed book)
19. Flurbiprofen is one of the non-steroidal anti-inflammatory drugs (NSAIDs). Examine the binding pocket for flurbiprofen shown below. Suggest reasonable choices for amino acids to bind to the drug at each of the three positions designated by the letters A, B and C. Briefly describe the non-covalent interaction that would occur between the drug and your chosen amino acid. (10 pts.)
Fa2014 Exam 1 (closed book)
10. Glycine is a neurotransmitter, in addition to being an amino acid. Yu and coworkers have studied the binding of glycine to the human glycine receptor (See Biochemistry 2014, DOI 10.1021/bi500815f). Examine the glycine binding pocket diagram shown below.
a) Yu and coworkers report that the mutation Lys200Ala substantially reduces the binding of glycine to the receptor protein. Would you expect Lys200 to be found at position A, B or C in the binding site? Briefly explain your reasoning. (8 pts.)
b) Suggest likely amino acids to be found at the remaining two positions that you didn’t discuss in part A. (6 pts.)
Fa2013 Exam 1 (closed book)
10. Examine the structure of the glycolytic metabolite 2-phosphoglycerate shown below.
a) In the spaces labeled A, B, and C, suggest the appropriate amino acids that would be used by a protein that binds 2-phosphoglycerate. (9 pts.)
b) What changes in positions A, B, and C would need to be made (or genetically engineered) to create a protein that binds benzoic acid instead of 2-phosphoglycerate. The structure of benzoic acid is shown below. (5 pts.)
Fa2012 Exam 1 (closed book)
9. Examine the structure of the cholesterol-binding pocket shown below. Label each position A, B and C, with the non-covalent force responsible for binding and suggest an amino acid that would provide the suggested force. If you choose hydrogen bonding, specify whether you are choosing a hydrogen bond or acceptor. (12 pts.)
Fa2010 Exam 1 (open book)
13. A compound called StemRegenin-1 (SR-1) that helps adult stem cells grow is under study for potential medical applications. SR-1 was recently shown to bind to the aryl hydrocarbon receptor (see Science 2010, 329, 1345). Examine the structure of SR-1 shown in the figure below. (12 pts.)
For each position, describe the intramolecular force responsible for binding and suggest amino acid that would provide the suggested force. If you choose hydrogen bonding, specify whether you are choosing a hydrogen bond or acceptor.
Position A
Position B
Position C
Fall 2009 Final Exam (closed book)
19. The non-steroidal anti-inflammatory drug indomethacin acts on the enzyme phospholipase A2. Examine the possible binding site shown below. For each position A, B, and C, suggest a reasonable choice for an amino acid that would help bind the drug.
Fall 2008 Final Exam (open book section)
22. o-Succinylbenzoyl-CoA synthetase has been identified as potential target for the development of new antibiotics. Yang Tian and coworkers have produced an inhibitor that binds to both the o-succinylbenzoyl (OSB) binding site and the ATP binding site at the same time (see Biochemistry 2008, 47, 12434-47).
Examine their proposed positioning of the inhibitor in the enzyme and suggest possible amino acids that would be responsible for the binding the inhibitor at positions A, B and C. For any proposed hydrogen bonding interactions, state whether the amino acid used would act as a hydrogen bond donor, acceptor or both.