A PLASMID-ENCODED DIHYDROFOLATE-REDUCTASE FROM TRIMETHOPRIM-RESISTANT BACTERIA HAS A NOVEL D-2-SYMMETRICAL ACTIVE-SITE

被引：78

作者：

NARAYANA, N

MATTHEWS, DA

HOWELL, EE

XUONG, NH

机构：

[1] AGOURON PHARMACEUT INC,SAN DIEGO,CA 92121

[2] UNIV TENNESSEE,DEPT BIOCHEM,KNOXVILLE,TN 37996

[3] UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093

[4] UNIV CALIF SAN DIEGO,DEPT PHYS,LA JOLLA,CA 92093

[5] UNIV CALIF SAN DIEGO,DEPT CHEM & BIOCHEM,LA JOLLA,CA 92093

来源：

NATURE STRUCTURAL BIOLOGY | 1995年 / 2卷 / 11期

关键词：

D O I：

10.1038/nsb1195-1018

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：

Bacteria expressing R67-plasmid encoded dihydrofolate reductase (R67 DHFR) exhibit high-level resistance to the antibiotic trimethoprim. Native R67 DHFR is a 34,000 M(r) homotetramer which exists in equilibrium with an inactive dimeric form. The structure of native R67 DHFR has now been solved at 1.7 Angstrom resolution and is unrelated to that of chromosomal DHFR, Homotetrameric R67 DHFR has an unusual pore, 25 Angstrom in length, passing through the middle of the molecule. Two folate molecules bind asymmetrically within the pore indicating that the enzyme's active site consists of symmetry related binding surfaces from all four identical units.

引用

页码：1018 / 1025

页数：8