Pak, Valeriy V., Koo, Min-Seon, Lee, Na-Ri, Oh, Su-Kyung, Kim, Myung-Sunny, Lee, Jong-Soo, Kwon, Dae-Young
언어
영어(ENG)
URL
https://www.earticle.net/Article/A78897
※ 원문제공기관과의 협약기간이 종료되어 열람이 제한될 수 있습니다.
원문정보
초록
영어
Synthesized Ile-Ala-Val-Pro (IAVP) peptide, which has the highest hypocholesterolemic effect among a number of synthesized derivatives of Ile-Ala-Val-Pro-Gly-Glu-Val-Ala (IAVPGEVA) isolated from 11S globulin of soy protein by pepsin digestion, was selected for investigation in the present study. Using a recombinant Syrian hamster 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), we studied in detail the inhibition of this enzyme by IAVP and compared the action of this peptide to that of lovastatin, a known competitive inhibitor of this enzyme. The concentration of IAVP required for 50% inhibition (IC50) of HMGR activity in given experimental conditions was340 uM . Kinetic analysis revealed that the studied peptide is a competitive inhibitor of HMGR with respect to both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) and nicotinamide adenine dinucleotide phosphate (NADPH), with an equilibrium constant of inhibitor binding (Ki = [K][I]/[KI] of 61±1.2 uM and 157±4.4 uM , respectively. At the same conditions, Ki and IC50 for lovastatin were 2.2±0.1 uM and 12.5 nM, respectively. Thus, the given peptide interacts with HMGR as a bisubstrate, consequently blocking access of both substrates to the active sites. The achieved results suggest the design of new peptide sequences having a higher relative affinity to binding sites of this enzyme and an enhancement of their hypocholesterolemic properties.
목차
Abstract Introduction Materials and Methods Results and Discussion Acknowledgments References