Vpliv polimorfizma posameznega nukleotida  rs 4880 na genu  sod2  na sekundarno strukturo encima manganove superoksid-dismutaze : magistrsko delo

Broz, Matic

| | SLO | ENG | Cookies and privacy

Bigger font | Smaller font

First page > Show document

Show document

Title:	Vpliv polimorfizma posameznega nukleotida rs 4880 na genu sod2 na sekundarno strukturo encima manganove superoksid-dismutaze : magistrsko delo
Authors:	ID Broz, Matic (Author) ID Bren, Urban (Mentor) More about this mentor... ID Furlan, Veronika (Comentor)
Files:	MAG_Broz_Matic_2019.pdf (2,13 MB) MD5: 14FAC2D7D6093095C8623531279B24C1 PID: 20.500.12556/dkum/e908ae0d-a27b-4a5f-86c5-97e4a0b3fa50
Language:	Slovenian
Work type:	Master's thesis/paper
Typology:	2.09 - Master's Thesis
Organization:	FKKT - Faculty of Chemistry and Chemical Engineering
Abstract:	Reaktivne kisikove spojine so reaktivni prosti radikali, ki nastajajo kot stranski produkt presnove kisika pri celičnem dihanju. Čeprav škodujejo celicam in povzročajo t.i. oksidativni stres, igrajo pomembno vlogo pri celični signalizaciji in v imunskem odzivu, zato je konstanta koncentracija teh molekul ključna za pravilno delovanje celic. V mitohondriju, največjem viru kisikovih prostih radikalov, deluje encim MnSOD, ki katalizira razgradnjo superoksidnega aniona. V magistrskem delu smo s pomočjo računalniških simulacij molekulske dinamike želeli ugotoviti, kako dimorfizem Ala16Val vpliva na sekundarno strukturo 24 aminokislin dolge mitohondrijske tarčne sekvence MnSOD, ki je ključna za uspešen transporta prekurzorske MnSOD v mitohondrijski matriks in posledično za uspešen transport MnSOD v mitohondrij, kjer le-ta opravlja svojo funkcijo. Za načrtovanje treh modelov obeh variant smo uporabili predpostavljeno strukturo iz literature in spletni orodji za določevanje sekundarne strukture peptidov PEPFOLD3 in Phyre2. S pomočjo programa PyMOL in spletnega orodja H++ smo pripravili vhodne datoteke za poganjanje simulacij molekulske dinamike s programskim paketom GROMOS++. Dobljeni rezultati kažejo, da sta najstabilnejša modela za obe varianti napovedana z orodjem Phyre2: dvakrat prekinjen α-heliks za alanin in neprekinjen α-heliks za valin, kot stabilna, pa sta se izkazala tudi modela, napovedana s PEPFOLD3. Rezultati za varianto z alaninom kažejo na α-heliks, katerega enkrat prekine zavoj. Rezultati za valin so deloma razdvojeni in kažejo, da je najbolj stabilen krajši α-heliks, kot ga je predvideval začetni model. Obe ugotovitvi sta tudi v skladu z literaturo, ki pravi, da imajo prekurzorske sekvence večinoma obliko amfifilnih α-heliksov. V svoji raziskavi smo ovrgli hipotezo, da sta strukturi, predpostavljeni v dosedanji literaturi, stabilni.
Keywords:	manganova superoksid-dismutaza, polimorfizem rs4880, mutacija Ala16Val, simulacije molekulske dinamike
Place of publishing:	Maribor
Place of performance:	Maribor
Publisher:	[M. Broz]
Year of publishing:	2019
Number of pages:	XIII, 60 str.
PID:	20.500.12556/DKUM-74707
UDC:	575.224(043.2)
COBISS.SI-ID:	22688790
NUK URN:	URN:SI:UM:DK:OHXVXCLM
Publication date in DKUM:	21.10.2019
Views:	1976
Downloads:	233
Metadata:
Categories:	KTFMB - FKKT
:	Copy citation

Average score:	(0 votes)
Your score:	Voting is allowed only for logged in users.
Share:

Hover the mouse pointer over a document title to show the abstract or click on the title to get all document metadata.

Licences

License:	CC BY-ND 4.0, Creative Commons Attribution-NoDerivatives 4.0 International

Link:	http://creativecommons.org/licenses/by-nd/4.0/
Description:	Under the NoDerivatives Creative Commons license one can take a work released under this license and re-distribute it, but it cannot be shared with others in adapted form, and credit must be provided to the author.
Licensing start date:	04.09.2019

Secondary language

Language:	English
Title:	The effect of single nucleotide polymorphism rs 4880 on sod2 gene on secondary structure of manganese superoxide-dismutase enzyme
Abstract:	Reactive oxygen species (ROS) are reactive free radicals that are formed as a by-product of oxygen metabolism in cellular respiration. Although ROS can damage cells and cause so-called oxidative stress, they play an important role in cell signaling and in the immune response, which makes maintaining a constant concentration of these molecules crucial for the proper functioning of cells. In the mitochondria, the largest source of oxygen free radicals, the enzyme MnSOD acts as a catalyst for the dismutation of the superoxide anion. In master's thesis, we aimed to determine through molecular dynamics simulations how Ala16Val dimorphism affects the secondary structure of the 24 amino acid MnSOD mitochondrial target sequence, which is crucial for successful transport of the precursor MnSOD into the mitochondrial matrix where it scavenges for superoxide anions. For both sequence variants, alanine and valine, three models were designed by using the structure determined in the literature and online tools (PEPFOLD3 and Phyre2) for determining the secondary structure of peptides. Using the program PyMOL and the H++ web tool, we have prepared input files for running molecular dynamics simulations with the GROMOS ++ software package. The obtained results indicate that the most stable models for both variants were predicted by the Phyre2 tool, a twice bend broken α-helix for alanine and unbroken α-helix for valine, however, the models predicted by PEPFOLD3 were comparable to Phyre2. The results indicate that the most stable secondary structure for alanine is a by a bend broken α-helix that extends across the most part of the peptide. The results for valine are divided but overall indicate a shorter α-helix than predicted by initial models. Both findings are in the agreement with the literature, which suggests that mitochondrial targeting sequences adopt an amphiphilic α-helixes. We disproved the hypothesis that the structures predicted in the literature till date are stable.
Keywords:	manganese superoxide-dismutase, polymorphism rs4880, mutation Ala16Val, simulations of molecular dynamics

Comments

Leave comment

You must log in to leave a comment.

Comments (0)

0 - 0 / 0

There are no comments!

Back