Author/Editor		Makovec, Tomaž
Title		Struktura in imunokemijske lastnosti NADPH-citokrom P450 reduktaze iz glive Rhizopus nigricans
Translated title		Structure and immunochemical properties of NADPH-cytochrome P450 reductase from fungus Rhizopus nigricans
Type		monografija
Place		Ljubljana
Publisher		Medicinska fakulteta
Publication year		2001
Volume		str. 101
Language		slo
Abstract		Cytochrome P450 (P450) -mediated conversion steps are suggested to be a part of many speciflc fungal biotransformation processes. A well-studied class of bioconversions carried out by fungal P450 enryme systems is the stereo-specific hydroxylation of pharmaceutically interesting compounds, especially progesterone. It is remarkable that all the Saccharomyces cerevisiae P450s are involved in housekeeping activities, while many P450s in fllamentous fungi are involved in nonessential detoxyfication reactions or the synthesis of complex secondary metabolites. The best studied P450-mediated reactions concem the degradation of polyaromatic hydrocarbons such as benz<a>pyrene, the biotransformataion of pharmaceutically important steroids like progesterone and lanosterol, and the assimilation of long chain alkanes. Most fungal hydroxylation systems identifled so far belong to type I rnonooxygenases and are expected to be located on endoplasmic reticulum. This systems are composed of two enrymes: NADPH-cytochrome P450 reductase (CPR) (EC 1.6.2.4) and P450. The function of CPR is to receive two electrons from NADPH and transfer žem sequentially to P450. The enzyme contains one molecule of both FAD and FMN. The transfer of electrons has been shown to occur in the order NADPH to FAD, then to FMN, and finally to P450. This sequential transfer of two electrons occurs by redox cycling between the one-electron-reduced enzyme and the three-electronreduced form. Structural studies with rat or rabbit liver CPR have revealed that CPR is an amphipathic protein containing a large hydrophilic catalytic domain. Limited proteolylis of microsomal CPR yields two major peptide fragments; flavin containing hydrophylic domain (70-72 kDa) that can reduce non-physiological, artificial electron acceptors such a cytochrome c (but not P450) and a small (5-6 kDa) N-terminal hydrophobic membrane domain which is required for P450 reduction. (Abstract truncated at 2000 characters)
Descriptors		RHIZOPUS CYTOCHROME P-450 CYTOCHROME REDUCTASES PROGESTERONE HYDROXYLATION IMMUNOCHEMISTRY AMINO ACID SEQUENCE