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master's thesis
Simulacije molekulske dinamike proteina MntR iz bakterije Mycobacterium tuberculosis
Zagreb: University of Zagreb, Faculty of Science, 2022. urn:nbn:hr:217:005298
Brajković, Mislav
University of Zagreb
Faculty of Science
Department of Biology

Institutional repository: Repository of the Faculty of Science

Cite this document

Brajković, M. (2022). Simulacije molekulske dinamike proteina MntR iz bakterije Mycobacterium tuberculosis (Master's thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:005298

Brajković, Mislav. "Simulacije molekulske dinamike proteina MntR iz bakterije Mycobacterium tuberculosis." Master's thesis, University of Zagreb, Faculty of Science, 2022. https://urn.nsk.hr/urn:nbn:hr:217:005298

Brajković, Mislav. "Simulacije molekulske dinamike proteina MntR iz bakterije Mycobacterium tuberculosis." Master's thesis, University of Zagreb, Faculty of Science, 2022. https://urn.nsk.hr/urn:nbn:hr:217:005298

Brajković, M. (2022). 'Simulacije molekulske dinamike proteina MntR iz bakterije Mycobacterium tuberculosis', Master's thesis, University of Zagreb, Faculty of Science, accessed 14 May 2024, https://urn.nsk.hr/urn:nbn:hr:217:005298

Brajković M. Simulacije molekulske dinamike proteina MntR iz bakterije Mycobacterium tuberculosis [Master's thesis]. Zagreb: University of Zagreb, Faculty of Science; 2022 [cited 2024 May 14] Available at: https://urn.nsk.hr/urn:nbn:hr:217:005298

M. Brajković, "Simulacije molekulske dinamike proteina MntR iz bakterije Mycobacterium tuberculosis", Master's thesis, University of Zagreb, Faculty of Science, Zagreb, 2022. Available at: https://urn.nsk.hr/urn:nbn:hr:217:005298

Metadata
TitleSimulacije molekulske dinamike proteina MntR iz bakterije Mycobacterium tuberculosis
Title (english)Molecular dynamics simulations of the MntR protein from the bacterium Mycobacterium tuberculosis
AuthorMislav Brajković
MentorBranimir Bertoša (mentor)
Committee memberBranimir Bertoša (predsjednik povjerenstva)
Committee memberIvana Ivančić Baće (član povjerenstva)
Committee memberMartina Šeruga Musić (član povjerenstva)
Committee memberDavor Kovačević (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Biology)
Zagreb
Defense date and country2022-01-27, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Biology
Abstract
Homodimerni protein MntR (engl. Manganese Transport Regulator) regulira unutarstaničnu koncentraciju Mn2+ iona u bakteriji Mycobacterium tuberculosis represijom gena za njihov unos. Ovaj protein stvara interakcije s DNA u holo formi (s vezanim manganom), a u apo formi (bez vezanog mangana) je neaktivan. Molekularni mehanizam aktivacije proteina za vezanje DNA nije u potpunosti razjašnjen. Kako bi se istražile razlike strukturnih i dinamičkih svojstava apo i holo strukture proteina, provedene su računalne simulacije molekulske dinamike (MD). Analizom MD simulacija ustanovljeno je da su DNA-vezujuće domene (domene HTH) i N-terminalni lanci proteina MntR međusobno bliže u simulacijama holo strukture u usporedbi s apo strukturom. Približavanje domena HTH mogući je mehanizam aktivacije proteina za vezanje molekule DNA, ali potrebne su dodatne simulacije i eksperimenti kako bi to potvrdili. Manganovi ioni uzrokovali su i smanjenje fleksibilnosti nekih αzavojnica tijekom MD simulacija ukazujući na još jednu razliku apo i holo forme. Pronađena je mreža nekovalentnih interakcija između domena HTH i FeoA. Rezultati MD simulacija pokazuju da je ta mreža interakcija neophodna u povezivanju domena HTH i FeoA, prekidanje te mreže interakcija dovodi do odvajanja tih domena. Također, prekid te mreže interakcija uzrokuje i približavanje domena HTH među podjedinicama proteina što moguće ima utjecaj sposobnost vezanja DNA.
Abstract (english)
MntR (Manganese Transport Regulator) is a homodimeric protein that regulates intracellular manganese ion concentration in the bacterium Mycobacterium tuberculosis by repressing the Mn2+ intake genes. As contrast to the inactive apo structure (without bound manganese ions), the holo structure (with bound manganese ions) of MntR can form interactions with DNA. The molecular mechanism by which MntR is activated for DNA binding is unknown. Molecular dynamics (MD) simulations were performed to compare structural and dynamical properties of apo and holo MntR structures. MD simulations revealed that DNA-binding domains (HTH domains) and N-terminal chains were closer in simulations of holo structure than in apo structure. This might improve DNA binding and could represent a mechanism of MntR activation. However, this hypothesis needs to be confirmed by additional MD simulations and experiments. Another distinction between apo and holo structures is that Mn2+ in holo structures causes a decrease of the flexibility of some α-helices. Analyses of MD simulations identified network of non-covalent interactions between the HTH and FeoA domains. Disruption of this network caused the HTH and FeoA domains to separate, proving its critical role in inter-domain communication. In addition, breaking of the interdomain interaction network also brought the HTH domains close together, which may have an impact on DNA binding.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:005298
Study programmeTitle: Molecular Biology
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2022-01-31 13:26:48