Hegde Subray S, Vetting Matthew W, Roderick Steven L, Mitchenall Lesley A, Maxwell Anthony, Takiff Howard E, Blanchard John S
Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Science. 2005 Jun 3;308(5727):1480-3. doi: 10.1126/science.1110699.
Fluoroquinolones are gaining increasing importance in the treatment of tuberculosis. The expression of MfpA, a member of the pentapeptide repeat family of proteins from Mycobacterium tuberculosis, causes resistance to ciprofloxacin and sparfloxacin. This protein binds to DNA gyrase and inhibits its activity. Its three-dimensional structure reveals a fold, which we have named the right-handed quadrilateral beta helix, that exhibits size, shape, and electrostatic similarity to B-form DNA. This represents a form of DNA mimicry and explains both its inhibitory effect on DNA gyrase and fluoroquinolone resistance resulting from the protein's expression in vivo.
氟喹诺酮类药物在结核病治疗中越来越重要。结核分枝杆菌五肽重复蛋白家族成员MfpA的表达会导致对环丙沙星和司帕沙星产生耐药性。这种蛋白质与DNA旋转酶结合并抑制其活性。其三维结构显示出一种折叠，我们将其命名为右手四边形β螺旋，它在大小、形状和静电方面与B型DNA相似。这代表了一种DNA模拟形式，并解释了其对DNA旋转酶的抑制作用以及该蛋白质在体内表达导致的氟喹诺酮耐药性。
