Dear Jan,
Is there a possibility for bifurcated salt bridges/H-bonds where the Asp
would be entrapped between the two arginines, in which case, repulsive
effects would not take place ?
Cheers,
Nadir Mrabet
Pr. Nadir T. Mrabet
Structural & Molecular Biochemistry
N-gere - INSERM U-954
University of Lorraine, Nancy
School of Sciences and Technologies
& School of Medicine
9, Avenue de la Foret de Haye, BP 184
54505 Vandoeuvre-les-Nancy Cedex
France
Phone: +33 (0)3.83.68.32.73
Fax: +33 (0)3.83.68.32.79
E-mail: Nadir.Mrabet <at> univ-lorraine.fr
On 08/10/2013 17:00, Jan van Agthoven wrote:
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, herman.schreu...@sanofi.com <herman.schreu...@sanofi.com>:
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:CCP4BB@JISCMAIL.AC.UK] Im Auftrag von Jan
van Agthoven
Gesendet: Montag, 7. Oktober 2013 22:47
An: CCP4BB@JISCMAIL.AC.UK
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
