Simulacije molekulske dinamike proteina MntR iz bakterije Halalkalibacterium halodurans

master's thesis

• Title (english): Molecular dynamics simulations of the MntR protein from the bacterium Halalkalibacterium halodurans
• Author: Ana Marija Knez
• Mentor: Branimir Bertoša (mentor)
• Committee member: Branimir Bertoša (predsjednik povjerenstva)
• Committee member: Ivana Ivančić Baće (član povjerenstva)
• Committee member: Martina Šeruga Musić (član povjerenstva)
• Committee member: Davor Kovačević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-02-17, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Ioni prijelaznih metala neizostavna su komponenta brojnih staničnih procesa živih organizama.
Ipak, prevelika stanična koncentracija metalnih iona može biti toksična za stanicu pa su neophodni
osjetljivi mehanizmi regulacije njihove stanične koncentracije. Protein MntR je transkripcijski
faktor koji sudjeluje u mehanizmu regulacije stanične koncentracije manganovih(II) iona u
bakteriji Halalkalibacterium halodurans. U otopini je prisutan kao homodimer koji se vezanjem
dva manganova(II) iona aktivira za vezanje na DNA te sprječava transkripciju gena za unos
manganovih(II) iona. Simulacijama molekulske dinamike (MD) istražene su razlike u strukturnim
i dinamičkim svojstvima proteina MntR u apo (bez vezanih manganovih(II) iona) i holo (s vezanim
manganovim(II) ionima) obliku. Analizom MD simulacija identificirane su konformacijske odlike
koje holo strukturi olakšavaju vezanje u dva susjedna velika utora molekule DNA. Pronađene su
nekovalentne interakcije koje potencijalno imaju važnu ulogu u molekulskom mehanizmu koji
dovodi do povećanja afiniteta MntR proteina prema DNA uslijed vezanja manganovih(II) iona.
Rezultati simulacija upućuju da prisustvo manganovih(II) iona u veznom mjestu proteina dovodi
do zamijene vodikove veze Arg72 i Asp111 s kation–π interakcijom između Arg72 i Trp107 što
se reflektira na savijanje α4 – zavojnice i udaljenost između DNA vezujućih domena. Računalni
rezultati uspoređeni su s literaturno dostupnim eksperimentalnim podacima.
Ključne riječi: homeostaza mangana, alosterička aktivacija, nekovalentna interakcija, vodikova
veza, kation-π interakcija

Abstract (english)

Transition metal ions are an indispensable component of numerous cellular processes of living
organisms. However, excessive cellular concentration of metal ions can be toxic to the cell, so
sensitive mechanisms of regulation of their cellular concentration are necessary. The MntR protein
is a transcription factor that participates in the mechanism of regulation of the cellular concentration
of manganese(II) ions in the bacterium Halalkalibacterium halodurans. In the solution, it is present
as a homodimer which, by binding two manganese(II) ions, is activated to bind to DNA and
prevents the transcription of genes for the intake of manganese(II) ions. Molecular dynamics (MD)
simulations were used to investigate the differences in the structural and dynamic properties of the
MntR protein in the apoprotein (without bound manganese(II) ions) and holoprotein (with bound
manganese(II) ions) form. The analysis of MD simulations identified conformational features that
facilitate the binding of the holoprotein in two adjacent large grooves of the DNA molecule. Noncovalent interactions were found that potentially play an important role in the molecular
mechanism that leads to an increase in the affinity of the MntR protein to DNA due to the binding
of manganese(II) ions. The simulation results suggest that the presence of manganese(II) ions in
the binding site of the protein leads to the replacement of the hydrogen bond between Arg72 and
Asp111 with a cation–π interaction between Arg72 and Trp107, which is reflected in the bending
of the α4 helix and the distance between the DNA binding domains. The computational results
were compared with experimental data available in the literature

• Keywords: homeostaza mangana; alosterička aktivacija; nekovalentna interakcija; vodikova veza; kation-π interakcija
• Keywords (english): manganese homeostasis; allosteric activation; non-covalent interaction; hydrogen bond; cation-π interaction
• Language: croatian
• URN:NBN: urn:nbn:hr:217:043353
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-03-13 09:47:13