Dear Herman,
The arginine of the antibody is approximately at same distance from
the arginine of the ligand then the aspartic acid of the receptor,
respectively 3.3 and 3.25 A. But you're right! This same aspartic acid
makes a salt bridge with the arginine of the ligand, when this one is
bound to the receptor. So presumably, the ligand loses one salt bridge
when the antibody binds to the ligand receptor complex.
What is troubling is that the ligand is bound to the receptor by many
other hydrogen bonds and salt bridges. Also, mutation of this aspartic
acid to alanine hasn't shown a dramatic effect on ligand binding. So I
was thinking about a double effect: repulsion + loss of one salt
bridge.
Best,
Jan
2013/10/8, [log in to unmask] <[log in to unmask]>:
> Dear Jan,
> since electrostatics go with one over distance-square, there may still be
> some electrostatic repulsion if the aspartic acid is further away as the
> arginine. Another question is, what happens with the arginine of the ligand
> in absence of the antibody? Does it then make a salt bridge with the
> aspartic acid of the receptor? I expect that losing an a salt-bridge
> interaction between ligand and receptor will cause a significant drop in
> affinity which may explain the effect of the antibody.
>
> Best,
> Herman
>
>
>
> -----Ursprüngliche Nachricht-----
> Von: CCP4 bulletin board [mailto:[log in to unmask]] Im Auftrag von Jan
> van Agthoven
> Gesendet: Montag, 7. Oktober 2013 22:47
> An: [log in to unmask]
> Betreff: [ccp4bb] repulsive effects of arginine
>
> Hi everyone,
> I'm working on structure of an antibody that inhibits a receptor. The
> antibody doesn't induce any conformational change in the receptor and
> doesn't bind the ligand binding site. If we superimpose the receptor with
> antibody and ligand the only hindrance we find is a electrostatic repulsion
> between two arginines (3.3A): one is part of the antibody and one is part of
> the ligand and involved in ligand binding. However the arginine coming from
> the antibody makes a salt bridge with an aspartic acid from the receptor.
> Does this neutralize it's charge? Can we still say that it has a repulsive
> effect?
> Thanks
>
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