20.500.12556/RUL-144329 Računalniška analiza primernosti encima MurC za načrtovanje novih protibakterijskih učinkovin Computational analysis of the MurC enzyme suitability for the design of new antibacterial agents Bakterijska odpornost na trenutno dostopna antibiotična zdravila je eden največjih problemov javnega zdravja. K njenemu pojavu prispevata neustrezna in/ali prekomerna uporaba antibiotikov ter upadel razvoj novih antibiotičnih zdravil v zadnjih letih. Zato je razvoj novih protibakterijskih učinkovin nujen, pri čemer ga je smiselno usmeriti na mehanizme, ki so za obstoj bakterij nujni, kot sta na primer proces celične delitve ali biosinteza bakterijskega peptidoglikana. Eden izmed encimov, ki igrajo ključno vlogo pri biosintezi peptidoglikana, je encim UDP-N-acetilmuramat-L-alanin ligaza ali MurC. V okviru magistrske naloge smo zato s pomočjo različnih bioinformacijskih orodij, podatkovnih baz in programov poskušali ugotoviti, ali je encim MurC primerna tarča za razvoj novih protibakterijskih učinkovin. Pri analizi encima smo se osredotočili na ključne lastnosti potencialne tarče, kot so esencialnost gena, evolucijska ohranjenost aminokislin in sposobnost za vezavo učinkovine. Ugotovili smo, da je encim MurC esencialen za 43 bakterijskih organizmov, od katerih so trije organizmi ESKAPE. S pomočjo spletnega orodja UniProt smo ugotovili, da je izmed bakterij, pri katerih je znana sekvenca encima MurC, 11,7 % patogenih. S pomočjo analize evolucijske ohranjenosti aminokislin, poizvedb o napovedi potencialnih vezavnih mest in poizvedb o interakcijah aminokislin smo identificirali osem aminokislinskih položajev, ki so najprimernejši za tarčno ciljanje z učinkovino. Ti aminokislinski položaji encima MurC so: 128, 129, 130, 131, 173, 326, 346 in 352. Bacterial resistance to currently available antibiotic medicines is one of the most serious public health problems. The inadequate and/or excessive use of antibiotics and the decline in the development of new antibiotic drugs in recent years contribute to this phenomenon. For this reason, the development of new antibacterial agents is necessary, and it is useful to focus this development on the mechanisms necessary for the existence of bacteria, such as the process of cell division or the biosynthesis of bacterial peptidoglycan. One of the enzymes that play a key role in the biosynthesis of peptidoglycan is the enzyme UDP-N-acetylmuramate-L-alanine ligase or MurC. As part of our master's thesis, we attempted to use various bioinformatics tools, databases and programmes to determine whether the MurC enzyme is a suitable target for the development of new antibacterial agents. In analysing the enzyme, we focused on key properties of the potential target, such as gene essentiality, evolutionary conservation of amino acids and druggability. We found that the MurC enzyme is essential for 43 bacterial organisms, three of which are ESKAPE organisms. Using the UniProt online tool, we found that of the bacteria for which the sequence of the MurC enzyme is known, 11.7% are pathogenic. Using amino acid evolutionary conservation analysis, queries to predict potential binding sites and queries on amino acid interactions, we identified 8 amino acid positions best suited for drug targeting. These amino acid positions of the MurC enzyme are: 128, 129, 130, 131, 173, 326, 346 and 352. MurC evolucijska ohranjenost esencialnost bioinformacijska orodja bakterijska rezistenca MurC evolutionary conservation essentiality bioinformatics tools bacterial resistance true false false Slovenski jezik Angleški jezik Magistrsko delo/naloga 2023-02-15 07:45:02 2023-02-15 07:45:11 2023-02-16 03:41:12 0000-00-00 00:00:00 2023 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1970-01-01 95019 14082.pdf 14082.pdf 1 5F3683F14A963072F7B289A6E1C3D36A a8dcadc1c86c5658c995ef01ede07ff251729abe9ab864a08bbfe5fe42405beb f777b731-acfb-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=166584 Fakulteta za farmacijo 0 0 0