Work

Predictive methods for computational metalloenzyme redesign – a test case with carboxypeptidase A

Year: 2016

Type: article

Abstract: -dependent carboxypeptidase A (CPA), and its mutant proteins, which are hypothesized to hydrolyze modified substrates. For the native CPA, we replicated the catalytic mechanism and the rate in close agreement with the experiment, giving validity to the QM/DMD predicted structure, the DFT mechanism, and the QTAIM assessment of catalytic activity. For most sequences of the modified substrate and tried CPA mutants, substantially worsened activity is predicted. However, for the substrate mutant that contains Asp instead of Phe at the C-terminus, one CPA mutant exhibits a reasonable activity, as predicted across the theoretical methods. CPA is a well-studied system, and here it serves as a testing ground for the offered methods.

Source: Physical Chemistry Chemical Physics

DOI: 10.1039/c6cp02247b

Authors: Crystal E. Valdez, Amanda Morgenstern, Mark E. Eberhart, Anastassia N. Alexandrova

Institutions: University of California, Los Angeles, University of California System, Colorado School of Mines, California Institute of Technology, California NanoSystems Institute

Language: English

Topic: Chemical Reaction Mechanisms

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green