5ADO: Crystal structure of the paraoxon-modified A.17 antibody FAB fragment - Light chain S35R mutant

Citation:
Abstract
In vitro selection of antibodies from large repertoires of immunoglobulin (Ig) combining sites using combinatorial libraries is a powerful tool, with great potential for generating in vivo scavengers for toxins. However, addition of a maturation function is necessary to enable these selected antibodies to more closely mimic the full mammalian immune response. We approached this goal using quantum mechanics/molecular mechanics (QM/MM) calculations to achieve maturation in silico. We preselected A17, an Ig template, from a naive library for its ability to disarm a toxic pesticide related to organophosphorus nerve agents. Virtual screening of 167,538 robotically generated mutants identified an optimum single point mutation, which experimentally boosted wild-type Ig scavenger performance by 170-fold. We validated the QM/MM predictions via kinetic analysis and crystal structures of mutant apo-A17 and covalently modified Ig, thereby identifying the displacement of one water molecule by an arginine as delivering this catalysis.
PDB ID: 5ADODownload
MMDB ID: 144634
PDB Deposition Date: 2015/8/21
Updated in MMDB: 2016/11
Experimental Method:
x-ray diffraction
Resolution: 1.55  Å
Source Organism:
Similar Structures:
Biological Unit for 5ADO: dimeric; determined by author and by software (PISA)
Molecular Components in 5ADO
Label Count Molecule
Proteins (2 molecules)
1
FAB A.17
Molecule annotation
1
FAB A.17
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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