Author/Editor		Breznik, Matej; Planinšek, Odon; Kikelj, Danijel
Title		Struktura aktivnih mest nekaterih serinskih proteaz kot osnova za načrtovanje inhibitorjev
Translated title		Structures of serine protease active sites as basis for rational design of inhibitors
Type		članek
Source		Farm Vestn
Vol. and No.		Letnik 51, št. 4
Publication year		2000
Volume		str. 547-52
Language		slo
Abstract		Serine proteases are widespread peptidases that have control over protein synthesis, their turnover and function, which enables them to regulate physiological processes such as digestion, blood coagulation, inflammation andimmune response. Typpicaly, serine proteases have active site clefts that are exposed to solvent permitting access to polypeptide chains of their nativesubstrates. Frequently their inhibitors are small flexible molecules that interact only with small regions of the enzyme. This leads to one of the major problems with designing inhibitors-obtaining selectivity. Availability of three-dimensional structure of proteases involving structiral information about its active site combined with molecular modeling allows rational design of selective inhibitors.
Summary		Serinske proteaze katalizirajo hidrolizo peptidne vezi ter sodelujejo v biokemičnih reakcijah, ki so del prebavnih procesov, strjevanja krvi, vnetnih procesov in imunskega odziva. V telesu uravnavajo mnogo fizioloških procesov in so zanimive s stališča razvoja novih zdravilnih ueinkovin. Posamezne serinske proteaze s podobno oblikovanim aktivnim mestom in enakim mehanizmom delovanja imajo lahko popolnoma različne funkcije. Aktivno mesto serinskih proteaz je navadno odprto proti topilu, dostop je omogoeen velikim polipeptidnim verigam, kot so njihovi naravni substrati. Spojine, ki modulirajo delovanje encimov, najpogosteje neproteinski inhibitorji, so navadno manjše in fleksibilnejše molekule, ki prekrivajo le majhen del encima. Ker je število interakcij z encimom manjše, se pojavi problem selektivnosti. Poznavanje trodimenzionalne strukture posamezne proteaze in s tem oblike in položaja aktivnega mesta omogoea racionalno načrtovanje selektivnih inhibitorjev.
Descriptors		SERINE PROTEINASES BINDING SITES SERINE PROTEINASE INHIBITORS CHYMOTRYPSIN TRYPSIN FACTOR XA THROMBIN