Defective enzyme retaining some function but not all

[sera2018]

I was doing an MCAT diagnostic test from kaplan. One of the topics was a mutation that caused an enzyme to lose only some of its function but retained most.

I'm confused in general how an enzyme can only lose some part of its function but not all of it. Doesn't losing some function indicate that the active site is somehow defective and this could cause its substrates to be more loosely connected? Does losing "some" function indicate simply a lower activity level?

If the structure of active site is therefore affected then I assumed that the alteration of the primary sequence is the cause and this indicated frameshift...

But kaplan says it's missense b/c an enzyme losing only part of its function indicates some changes to the AA sequence but not all. Frameshift would therefore be too big of a damage for the enzyme even work anymore.

So what is the degree of mutation that would allow an enzyme to retain some function? It stills seems arbitrary to me b/c what if a nonsense mutation stopped the protein at the very end of the sequence but it didn't affect active site? Wouldn't the enzyme still have some function?

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[aldol16]

The lines aren't really clear cut. It's more of a critical reasoning question where you have to determine the mutation type that most likely would cause only a partial loss of function rather than a full loss of function. In general, mutating only one residue will only result in partial loss of function because the rest of the active site is intact. So for instance, say you have an Asp that stabilizes a positive charge on your substrate that helps the substrate bind to the active site. If you mutate that away, the substrate can still bind and undergo catalysis - it'll just bind less well and therefore you're going to see decreased enzyme function. On the other hand, a frameshift would drastically change the active site, which would more likely would cause the enzyme to lose all function.

Of course, you can find specific instances of either in which you see the opposite effect. For instance, mutating away a serine in a serine protease. That would cause some drastic reduction/loss in activity. Or a frameshift that happens in a part in the primary sequence that only affects a small part of the active site causing only partial loss of function. But in general, you would expect mutation of only one or a few residues to not change function much whereas mutation of a lot of residues would cause loss of function.

 

[sera2018]

Thanks, that makes sense!