定制催化位点腔中的免疫球蛋白。
Immucillins in custom catalytic-site cavities.
作者信息
Murkin Andrew S, Clinch Keith, Mason Jennifer M, Tyler Peter C, Schramm Vern L
机构信息
Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
出版信息
Bioorg Med Chem Lett. 2008 Nov 15;18(22):5900-3. doi: 10.1016/j.bmcl.2008.08.047. Epub 2008 Aug 19.
Abstract
Neighboring-group participation in the reaction catalyzed by purine nucleoside phosphorylase involves a compression mode between the 5'- and 4'-ribosyl oxygens, facilitated by His257. The His257Gly mutant opens a space in the catalytic site. Hydrophobic 5'-substituted Immucillins are transition-state analogue inhibitors of this mutant enzyme. Dissociation constants as low as 2pM are achieved, with K(m)/K(d) as high as 400,000,000.
摘要
嘌呤核苷磷酸化酶催化的反应中，邻基参与涉及由His257促进的5'-和4'-核糖氧基之间的压缩模式。His257Gly突变体在催化位点打开了一个空间。疏水的5'-取代的免疫菌素是这种突变酶的过渡态类似物抑制剂。解离常数低至2pM，K(m)/K(d)高达400,000,000。
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