interesting biochem question

[constructor]

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does anyone know how a mutation that changes a single amino acid that's not close to the active site of an enzyme can lower both Vmax and Km? i know that uncompetitive inhibition is the only kind of inhibition where both Vmax and Km are lowered, but how does that idea apply here where you don't have an inhibitor but a mutation that results in the same effect? or does it apply?

 

[indo]

There are a couple histidine residues in hemoglobin that if switched to another AA will change the rates. One of them prevents CO from binding semi-permanently. That is the only example I can think of right now.

I suppose structural changes far from the active site could change the shape of the active site enough to cause the changes you mentioned.

 

[ChyLn]

Mutations in areas outside of the active site can often cause changes in enzymatic activity by affecting protein folding and/or the binding of cofactors and other proteins that may be necessary for function.

 

[udbluehen]

does anyone know how a mutation that changes a single amino acid that's not close to the active site of an enzyme can lower both Vmax and Km? i know that uncompetitive inhibition is the only kind of inhibition where both Vmax and Km are lowered, but how does that idea apply here where you don't have an inhibitor but a mutation that results in the same effect? or does it apply?

I think you're thinking right along the lines of an uncompetitive inhibitor. Just as an uncompetitive inhibitor can bind to an allosteric site to alter protein structure or preferentially stabilize a protein conformation to lower both Km and vmax, a mutation could have a similar effect on protein structure. Remember that allosteric inhibitors simply stabilize an "inactive" conformation of a protein relative to the "active" conformation, and a change in protein struture remote from the active site could have a similar effect resulting in a change in kinetic parameters analagous to that of an uncompetitive inhibitor.