difference between Asp and Glu? - (Nov/15/2004 )

Hi, everyone

I am making some mutants of a Calcium channel, mainly interested in a Asp residue located in S4-S5 linker. When this Asp was mutated into Glu, the channel lost its function.

Given both Asp and Glu are negatively charged, and have similiar molecular weight, I wonder why this subtle change killed the channel. Does anybody know what is the major difference between these two amino acids, in terms of biochemistry properties, strutural biology or whatever?

Thank you very much indeed.

Fanning

Hi there!!
Even though aspartic acid (or aspartate) has a lower pKa than glutamic acid (glutamate) (3.9 vs 4.07), I'd put my money on steric inderance. Glu is a little "bigger" than Asp, and can then block some important sites that are beside the residue. Molecular weight of residues don't really matter. I too work on a calcium channel (TRPC), and I believe that your loss of function may be related with a loss of binding with a essential protein.

Simon