AAMC Sample C/P Q49

[Life2dmax]

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Need some help on number 49.

It asks about the following molecule

It says the stabilization of pantothenate in Pantothenate Kinases is most likely due to an active site
a. arginine b. asparagine c. aspartate or d. glutamine

I chose A. because I thought the postive charge will help stabilize the negatives. The answer is apparently C since "aspartate has the necessary carboxylate side chain." Can anyone explain this?

 

[aldol16]

Your B and C are the same. Are you given any other information in the context of the passage? If we're talking about a specific reaction at the active site, then aspartate is could serve as a general base. For instance, the substrate carboxylic acid could have a high pKa but when it binds to the active site, the pKa lowers such that the aspartate can deprotonate the carboxylic acid, which activates it to attack on a phosphate.

 

[Life2dmax]

Your B and C are the same. Are you given any other information in the context of the passage? If we're talking about a specific reaction at the active site, then aspartate is could serve as a general base. For instance, the substrate carboxylic acid could have a high pKa but when it binds to the active site, the pKa lowers such that the aspartate can deprotonate the carboxylic acid, which activates it to attack on a phosphate.

Oops B was asparagine but it didnt matter much

Hm. it just says that PanK catalyzes the phosphorylation of pantothenate to form phosphopantothenate, uses ATP. I'm not great at chem but I never thought about aspartate acting as a base..

I'd post the entire passage but I dont think i'm allowed to so if someone else sees something I'm missing let me know

 

[aldol16]

Yeah, I mean, I agree with your thought process but you might want to re-read it just to make sure you're not missing anything. Aspartate is a common base that enzymes use - for instance, it's the crucial residue in HIV protease.

 

[aldol16]

Hm. it just says that PanK catalyzes the phosphorylation of pantothenate to form phosphopantothenate, uses ATP. I'm not great at chem but I never thought about aspartate acting as a base..

I'd post the entire passage but I dont think i'm allowed to so if someone else sees something I'm missing let me know

I got it. You missed the part in the passage where it said the substrate was stabilized by a carboxylate group on the enzyme.

 

[NextStepTutor_3]

Yes, this one is entirely passage-based! This type of question (where you're asked to predict which amino acid residues would be found at an active site) is very common. I like to use the strategy "the more complex / large / unfamiliar the molecule, the more likely it is that the passage will give the info you need." Just think about the structure of pantothenate - sure, it'll be negative at physiological pH, but there's a lot of other stuff going on there (hydroxyl groups, etc.). We can't possibly know that they're referring solely to its negative nature unless they tell us (and in this case, of course, they aren't).

Even the next question (#50) is really similar, except they're asking which residues would stabilize ADP. Again, we COULD jump to the conclusion that ADP is negative, so we're looking for positive residues (and that ends up being correct in this case). But, again, it's safer to consult the passage. For that one, the very last sentence says that ADP is stabilized by "ionic interactions" - so we know that it's safe to think about charge alone in this case.