B2.023 Mutations that Alter Proteins: A Variety of Outcomes Flashcards Preview

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Flashcards in B2.023 Mutations that Alter Proteins: A Variety of Outcomes Deck (15):

what kinds of protein parameters can mutations alter?

folding/stability, concentration, location, post-translational modification, function


what factors affect alteration of protein concentration?

gene expression and protein degradation


what measure is affected by protein concentration?

vmax of catalysis or transport


what example was discussed with reference to post translational modifications of proteins?

cleaving of trypsinogen by enteropeptidase in small intestine to activate it into trypsin

trypsin then catalyzes activation of other enzymes


how do proteins bind to ligands?

specific amino acid interactionds, side chain or backbone


how can mutations alter binding?

affinity (how tightly it binds)
specificity (which lingand is bound most tightly)


how do we quantify binding affinities?

association reaction and dissociation reaction constants Ka and Kd


why is Kd particularly useful?

Kd=[L] when [P] = [PL] so you can tell how much ligand needs to be present to bind 50% of the protein (units M)


how do you plot ligand/protein binding?

[ligand] vs fraction bound
can be linear (hyperbolic shape) or log (sigmoidal shape)


how can a mutation in amino acid physically decrease binding stability in vitamin D resistant rickets?

if a smaller amino acid is subbed, lacks stabilizing interaction


how can a mutation in an ion channel protein affect the heart?

long QT syndrome can result from Na+ channels not opening/closing properly


how does HIV resist drugs?

mutations in the HIV protease can inhibit the drugs ability to bind to the active site, making the drug ineffective against that from of HIV


how do we get around drug resistance in HIV protease?

treat HIV with a cocktail of 8 drugs


what is protein moonlighting?

proteins can have more than one function


what are 4 complicating factors in the study of protein function?

1. moonlighting
2. normal polymorphisms can interact differently with the environment
3. environment includes other proteins
-partners can have exacerbating or compensatory mutations
4.current computer algorithms predict good/bad for missense mutations, but risk could be intermediate