Računalno istraživanje kompleksa DNA i MntR proteina iz bakterije Bacillus subtilis

master's thesis

• Title (english): Computational study DNA in complex with the MntR protein from the bacterium Bacillus subtilis
• Author: Michaela Batković
• Mentor: Branimir Bertoša (mentor)
• Committee member: Branimir Bertoša (predsjednik povjerenstva)
• Committee member: Ivan Kodrin (član povjerenstva)
• Committee member: Marko Močibob (član povjerenstva)
• Committee member: Davor Kovačević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2023-09-27, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Transkripcijski faktor MntR (engl. Manganese Transport Regulator) homodimerni je protein
odgovoran za regulaciju homeostaze manganovih iona u bakteriji Bacillus subtilis. Kada je u
svojoj holo-formi, to jest kada su unutarstanične koncentracije manganovih iona previsoke,
transkripcijski faktor MntR se veže na ciljnu DNA i ponaša kao represor. Postoji nekoliko
mehanizama kojima se proteini vežu na DNA, međutim, mehanizam vezanja proteina MntR na
svoju ciljnu DNA nije razjašnjen. U ovom diplomskom radu provedeno je računalno
istraživanje koje za cilj ima doprinjeti razumijevanju interakcija između transkripcijskog
faktora MntR i njegove ciljne DNA sekvence. Rezultati simulacija molekulske dinamike (MD)
kompleksa DNA-MntR ukazuju da će doći do odvajanja sastavnica kompleksa ukoliko
zavojnica α3 proteina, odgovorna za prepoznavanje palindromskog slijeda ciljne DNA, nije
položena u blizini središta palindromskog slijeda TTT/AAA pri čemu će posljedično doći do
značajnih fluktuacija molekule DNA. U suprotnom slučaju, dolazi do stvaranja specifičnih
vodikovih veza između proteina i DNA, te su te vodikove veze zastupljene većinu trajanja
simulacije, pri čemu dodatno dolazi i do otvaranja velikog utora.

Abstract (english)

The transcription factor MntR ( Manganese Transport Regulator) is a homodimeric protein in
Bacillus subtilis responsible for the regulation of manganese homeostasis. When in its holoform, that is when the intracellular concentrations of managanese ions are too high, the
transcription factor MntR binds on its target DNA and acts as a repressor. There are few binding
mechanisms by which proteins bind to DNA. However, the one by which our protein of interest
binds to its target DNA is still unknown. In this Diploma Thesis a computational study was
carried out with the aim to contribute to the understanding of the interactions between the
transcription factor MntR and its target DNA sequence. Molecular dynamics (MD) simualtions
revealed that the components of the DNA-MntR complex will seperate if the recognition helix
α3 of the protein is not placed near the center of the palindrome TTT/AAA which will result in
significant fluctuations of the DNA molecule. In the opposite case, during the whole simualtion
specific hydogen bonds are formed accompanied with major groove opening.

• Keywords: homeostaza; metaloregulacija; molekulska dinamika; protein MntR
• Keywords (english): homeostasis; metaloregulation; molecular dynamics; MntR protein
• Language: croatian
• URN:NBN: urn:nbn:hr:217:725506
• Project: Number: IP-2020-02-3446; Title: Manganovi metalosenzori; Title: Manganese Metallosensors; Acronym: MaMes; Leader: Branimir Bertoša; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-10-13 09:56:09