Results - Details
Search command : Author="Γανωτάκης"
And Author="Δημήτριος"
Current Record: 1 of 101
|
Identifier |
000466068 |
Title |
Exploring SecA conformation dynamics for the development of effective antibiotics |
Alternative Title |
Διερεύνηση της δυναμικής διαμόρφωσης της SecA για την ανάπτυξη αποτελεσματικών αντιβιοτικών |
Author
|
Γιώτας, Εμμανουήλ Π.
|
Thesis advisor
|
Ελευθεριάδης, Νικόλαος
|
Reviewer
|
Παυλίδης, Ιωάννης
Γανωτάκης, Δημήτριος
|
Abstract |
SecA is a motor protein in prokaryotic cells, which participates in the
secretion mechanism of pre-proteins outside the cell. It is a crucial partner to
Sec pathway and essential for bacteria survival. The inhibition of SecA’ s activity
is believed to have a pivotal role in the discovery of new antibiotics. SecA is a
promising drug target as it is vital for the bacteria and there is no human
counterpart.
In this thesis, SecA was produced and purified, and its ATPase activity
was used to identify potent inhibitors. A high throughput protocol based on
Malachite Green was developed and used to screen more than 100 novel
compounds with different properties. The inhibitory concentration was
measured for the four most promising compounds and the IC50 values varied
from 160 μΜ to 2 mM . The most effective compound, MZ102, used for kinetic
studies to evaluate the inhibition type, which found to be competitive. Also,
molecular modelling experiments were performed to find the interactions of the
best compound inside the ATP binding pocket of the protein, which shown that
MZ102 and ATP occupy the same space between NBD1 and NBD2. SmFRET
was used to study protein dynamics, and previous findings verified the protocol
that was used. Finally, the effect of MZ102 in protein dynamics was
investigated, using smFRET, which seemed to slightly affect the monomer state
of the protein.
|
Language |
English |
Subject |
Enzyme kinetics |
|
Inhibitors |
|
Novel antibiotics |
|
smFRET |
|
Αναστολείς |
|
Καινοτόμα αντιβιοτικά |
|
Κινητική ενζύμων |
Issue date |
2024-07-19 |
Collection
|
School/Department--School of Sciences and Engineering--Department of Chemistry--Post-graduate theses
|
|
Type of Work--Post-graduate theses
|
Permanent Link |
https://elocus.lib.uoc.gr//dlib/c/4/4/metadata-dlib-1720773276-162543-14672.tkl
|
Views |
477 |