3-HYDROXY-3-METHYLGLUTARYLDITHIO-COENZYME-A - A POTENT INHIBITOR OF PSEUDOMONAS-MEVALONII HMG-COA REDUCTASE

被引:8
作者
WRENSFORD, LV [1 ]
RODWELL, VW [1 ]
ANDERSON, VE [1 ]
机构
[1] PURDUE UNIV,DEPT BIOCHEM,W LAFAYETTE,IN 47907
来源
BIOCHEMICAL MEDICINE AND METABOLIC BIOLOGY | 1991年 / 45卷 / 02期
关键词
D O I
10.1016/0885-4505(91)90022-D
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
3-Hydroxy-3-methyl-1-thionoglutaryl-coenzyme A, a dithioester analog of 3-hydroxy-3-methylglutaryl-CoA, has been enzymatically synthesized using the HMG-CoA synthase catalyzed condensation of acetyl-CoA with 3-oxo-1-thionobutyryl-CoA. HMGdithio-CoA is a potent inhibitor of Pseudomonas mevalonii HMG-CoA reductase. Inhibition was mainly competitive with respect to HMG-CoA with a Kis of 0.086 ± .01 μm and noncompetitive with respect to NADH with a Kis of 3.7 ± 1.5 μm and a Kii of 0.65 ± .05 μm in the presence of 110 μm (R,S)-HMG-CoA. © 1991.
引用
收藏
页码:204 / 208
页数:5
相关论文
共 14 条
[1]  
ANDERSON VE, 1990, J BIOL CHEM, V265, P6255
[2]   CLONING, SEQUENCING, AND OVEREXPRESSION OF MVAA, WHICH ENCODES PSEUDOMONAS-MEVALONII 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE [J].
BEACH, MJ ;
RODWELL, VW .
JOURNAL OF BACTERIOLOGY, 1989, 171 (06) :2994-3001
[3]  
GIL G, 1986, J BIOL CHEM, V261, P3710
[4]  
GRUNDY SM, 1988, NEW ENGL J MED, V319, P24
[5]   3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE INHIBITORS .2. STRUCTURAL MODIFICATION OF 7-(SUBSTITUTED ARYL)-3,5-DIHYDROXY-6-HEPTENOIC ACIDS AND THEIR LACTONE DERIVATIVES [J].
HOFFMAN, WF ;
ALBERTS, AW ;
CRAGOE, EJ ;
DEANA, AA ;
EVANS, BE ;
GILFILLAN, JL ;
GOULD, NP ;
HUFF, JW ;
NOVELLO, FC ;
PRUGH, JD ;
RITTLE, KE ;
SMITH, RL ;
STOKKER, GE ;
WILLARD, AK .
JOURNAL OF MEDICINAL CHEMISTRY, 1986, 29 (02) :159-169
[6]  
JORDANSTARCK TC, 1989, J BIOL CHEM, V264, P913
[7]  
KENNELLY PJ, 1985, J LIPID RES, V26, P903
[8]   3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A SYNTHASE FROM OX LIVER - PURIFICATION, MOLECULAR AND CATALYTIC PROPERTIES [J].
LOWE, DM ;
TUBBS, PK .
BIOCHEMICAL JOURNAL, 1985, 227 (02) :591-599
[9]   SCHWEFEL-HETEROCYCLEN UND VORSTUFEN .59. CLEMMENSEN-REDUKTION UND HALBSTUFENPOTENTIALE EINIGER THIOCARBONSAUREN UND ABKOMMLINGE [J].
MAYER, R ;
SCHEITHAUER, S ;
KUNZ, D .
CHEMISCHE BERICHTE-RECUEIL, 1966, 99 (04) :1393-+
[10]  
MEIJER J, 1974, RECL TRAV CHIM PAY B, V93, P242