Tip II topoizomeraza
Tip II topoizomeraze presecaju ova lanca DNK heliksa simultano radi upravljanja zamršenjem DNK i supernamotavanjima.[1][2] One koriste hidrolizu ATP-a, za razliku od tip I topoizomeraza. U tom procesu, ovi enzimi menjanju koeficijent povezivanja cirkularne DNK za +/-2.
Funkcija[uredi - уреди | uredi izvor]
Nakon presecanja, krajevi DNK se razdvajaju, i drugi DNK dupleks se propušta kroz presek. Nakon prolaza, presečena DNK se ponovo ligira. Ova rekcija omogućava tip II topoizomerazama da povećaju ili smanje koeficijent povezivanje DNK petlje za 2 jedinice, i promoviše hromozomsko razmršavanje.[3]
Inhibicija[uredi - уреди | uredi izvor]
Mali molekuli čija biološka meta je tip II topoizomeraza se dele u dve klase: inhibitore i otrove.
- Inhibitori tipa II topoizomeraze su između ostalih HU-331, ICRF-187, ICRF-193, i mitindomid. Ti molekuli inhibiraju dejstvo ATPaze putem nekompetitivne inhibicije ATP-a. To je pokazano putem strukturnih (Classen et al. Proceedings of the National Academy of Science, 2005) u biohemijskih studija.
- Otrovi tip II topoizomeraza su etopozid, novobiocin, hinolon (uključujući ciprofloksacin), i tenipozid. Biološka meta ovih malih molekula je DNA-proteinski kompleks. Neki od tih molekula dovode do povećanog presecanja, dok drugi puput etopozida, inhibiraju religaciju.
Eksperimentalni antitumorski lek m-AMSA (4'-(9'-akridinilamino)metanesulfon-m-anizidid) takođe inhibira tip 2 topoizomerazu.[4]
Reference[uredi - уреди | uredi izvor]
- ↑ Champoux JJ (2001). "DNA topoisomerases: structure, function, and mechanism". Annu. Rev. Biochem. 70: 369–413. PMID 11395412. doi:10.1146/annurev.biochem.70.1.369.
- ↑ "National Academy of Sciences: NAS Award in Molecular Biology". National Academy of Science. http://www.nasonline.org/site/PageServer?pagename=AWARDS_molbio. pristupljeno 07. 01. 2009..
- ↑ Wang, J.C. Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol. 2002 Jun;3(6):430-40.
- ↑ Willmore E, de Caux S, Sunter NJ et al. (2004). "A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia". Blood 103 (12): 4659–65. PMID 15010369. doi:10.1182/blood-2003-07-2527.
Literatura[uredi - уреди | uredi izvor]
- Nicholas C. Price, Lewis Stevens (1999). Fundamentals of Enzymology: The Cell and Molecular Biology of Catalytic Proteins (Third izd.). USA: Oxford University Press. ISBN 019850229X. http://books.google.com/books/about/Fundamentals_of_enzymology.html?id=8uvwAAAAMAAJ.
- Eric J. Toone (2006). Advances in Enzymology and Related Areas of Molecular Biology, Protein Evolution (Volume 75 izd.). Wiley-Interscience. ISBN 0471205036. http://books.google.com/books/about/Advances_in_Enzymology_and_Related_Areas.html?id=Pmh8yToeuloC.
- Branden C, Tooze J.. Introduction to Protein Structure. New York, NY: Garland Publishing. ISBN: 0-8153-2305-0. http://www.garlandscience.com/textbooks/0815323042.asp?type=reviews.
- Irwin H. Segel. Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems (Book 44 izd.). Wiley Classics Library. ISBN 0471303097. http://books.google.com/books/about/Enzyme_Kinetics.html?id=T60oAAAAYAAJ.
- Robert A. Copeland (2013). Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists (2nd izd.). Wiley-Interscience. ISBN 111848813X. http://books.google.com/books/about/Evaluation_of_Enzyme_Inhibitors_in_Drug.html?id=l2rMy8QNUk0C.
- Gerhard Michal, Dietmar Schomburg (2012). Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology (2nd izd.). Wiley. ISBN 0470146842. http://books.google.com/books/about/Biochemical_pathways.html?id=081qAAAAMAAJ.
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