Rational design and engineering of enzyme gates (BIOGATE)
- Kód projektu
- Období řešení
- 3/2014 - 12/2016
- Investor / Programový rámec / typ projektu
- Jihomoravský kraj
- Fakulta / Pracoviště MU
- Přírodovědecká fakulta
Gates are structural features that control key functions in various biological systems, from enzymes, ion channels, to protein complexes, etc. In spite of their importance, the knowledge about their structure and function is still limited, and to date there have been no attempts to rationally construct them in order to improve protein properties.
In this project, we propose to develop novel concepts and methods for engineering enzyme properties by de novo design of gates. For that purpose, the haloalkane dehalogenases will be used as model enzymes, representing a wide class of enzymes characterized by a buried active site connected to the surface by tunnels. These are bacterial enzymes that catalyze the hydrolysis of a wide variety of halogenated organic compounds into the corresponding alcohols. This property makes them very interesting for a number of technological applications, such as bioremediation, biocatalysis, and biosensors. Redesign of these tunnels has been accomplished in previous works and has proven successful to increase enzyme activity, enantioselectivity and stability.
Herein, through a systematic theoretical study, we will investigate the dynamics of the tunnels and their gates. In the next step, we will rationally design new gates and optimize their function, in order to maximize the reaction rate. This procedure will allow us to design and experimentally produce mutant enzymes with improved catalytic properties. With this challenging project, we expect to deliver new concepts and methods of protein engineering which will be applicable to a wide range of technologically important enzymes.
Počet publikací: 5