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BMS2062 - Introduction to bioinformatics S2 2025

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Consider the figure below, which shows comparison of an enzyme's complex with the coenzyme NAD+ (shown as orange sticks in the image below, with oxygen atoms in red and nitrogen atoms in blue) and its substrate (shown as green sticks in the image below). These data suggest that upon substrate binding, the loop comprising residues 236-246 closes over the active site, turning into a helix that keeps the substrate and reaction intermediates in place until the reaction is complete. If you perform sequence alignment of this enzyme with enzymes that catalyse the same reaction in other species, and plot the conserved residues onto the its 3D structure. The conserved residues within the 236 to 246 region will mostly likely:

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A domain with the same fold can be found in many different multi-domain proteins. These conserved domains, when present in distinct proteins, can be expected to:
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You are undertaking a research project in the lab that studies mutations in proteins of medical importance. You have been assigned to a project on an enzyme called sortase. When incubated with a polypeptide containing the LPXTG motif, it cleaves the peptide bond between the threonine (T) and the glycine (G), as shown in the Figure below. 

The Figure also shows that the mechanism of catalysis of this enzyme involves a direct transfer of an electron from the side chain of Cys184 to the peptide substrate, which results in the cleavage of the peptide bond in the substrate. 

What would be the most likely effect of a missense mutation resulting in a Cys184His substitution on the enzyme's activity?

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Individuals

who have brain creatine deficiency display intellectual disability. Sequencing

of exons in such individuals revealed that the brain creatine deficiency is

linked to an inborn genetic defect: such individuals are homozygous for a G→A

transition at nucleotide

position 9297

within exon 9 of the gene

encoding AGAT (see Figure below).

Which of

the following options provides the best explanation for why this mutation

causes disease?

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During exercise, a substance called creatine phosphate is used to

replenish ATP in the muscle. An enzyme called arginine:glycine amidinotransferase

(AGAT) is responsible for the first step in the biosynthesis of creatine. This

enzyme catalyses the transfer of an amidino group from arginine to glycine to

produce ornithine and guanidinoacetic acid.

Analysis of the structure of this enzyme bound to one of its

substrates, arginine, revealed the location of the active site and interactions

that stabilise the arginine molecule bound in the active site. The figure below

shows schematic representations of these interactions, and the impact of

different amino acid substitutions on the enzymatic activity.

Note that distances are shown in nm.

Taking into account the information presented in

the table, which residues are likely to be the catalytic residues that are

directly involved in the breaking and formation of bonds in the reaction

catalysed by this enzyme?

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You work in the drug development division of a large pharmaceutical company. The current commercially available medicine for a heart condition works as an inhibitor of a beta receptor, which it binds to with the dissociation constant (Kd) of 10 nM. You designed a new drug candidate. To measure the binding affinity between the receptor and the drug candidate (ligand), you incubated the receptor with the ligand at various concentrations, and measured the fraction of receptor bound. The results are presented in the graph below. What is the value of the dissociation constant (Kd) for the new drug candidate, and did you succeed in designing a candidate that binds stronger than the available drug?

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Dr Elisa Seaborn, who is a protein researcher, is studying how alpha helices and beta sheets are arranged in space to form a protein’s functional shape. Which level of protein structure is she investigating?
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The protein shown in the image above is phenylalanine hydroxylase. Which types of protein structure does it possess?
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7. How does the biotype classification of cancer affect how we treat patients?
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You compare JET mRNA levels in normal and tumour tissues and find a significant increase in tumour samples. Which of the following best explains this result?
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