A Noncleavable Retro-Binding Peptide That Spans the Substrate Binding Cleft of Serine Proteases. Atomic Structure of Nazumamide A: Human Thrombin

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• 作者：Vicki L. Nienaber and Eugene C. Amparo
• 刊名：Journal of the American Chemical Society
• 出版年：1996
• 出版时间：July 24, 1996
• 年：1996
• 卷：118
• 期：29
• 页码：6807 - 6810
• 全文大小：151K
• 年卷期：v.118,no.29(July 24, 1996)
• ISSN：1520-5126

文摘

The 2.0 Å resolution crystal structure of the retro-bindingnatural product nazumamide A (NAZA) complexedwith human thrombin is presented. The crystal structure shows thatthe retro-binding nazumamide A is noncleavableand extends into the prime end of the substrate binding cleft. Thedata suggest ideas for SAR and combinatorialmodification of nazumamide A to create a second generation ofnazumamide-like compounds which are potent andspecific for human thrombin. This crystal structure indicates thatfresh ideas for the generation of novel and specificinhibitors may arise from examining weak binding compounds.Additionally, the crystal structure demonstrates theutility of crystallographic analysis of natural product:proteincomplexes.