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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?
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 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?
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.
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?
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?