7rmr
Crystal structure of [I11L]cycloviolacin O2
Structural highlights
FunctionCYO2_VIOOD Probably participates in a plant defense mechanism. Has strong cytotoxic activity against a variety of drug-resistant and drug-sensitive human tumor cell lines, and against primary chronic lymphocytic leukemia and ovarian carcinoma cells. Has weaker cytotoxic activity against normal lymphocytes. Has hemolytic activity.[1] [2] Publication Abstract from PubMedCyclotides have attracted great interest as drug design scaffolds because of their unique cyclic cystine knotted topology. They are classified into three subfamilies, among which the bracelet subfamily represents the majority and comprises the most bioactive cyclotides, but are the most poorly utilized in drug design applications. A long-standing challenge has been the very low in vitro folding yields of bracelets, hampering efforts to characterize their structures and activities. Herein, we report substantial increases in bracelet folding yields enabled by a single point mutation of residue Ile-11 to Leu or Gly. We applied this discovery to synthesize mirror image enantiomers and used quasi-racemic crystallography to elucidate the first crystal structures of bracelet cyclotides. This study provides a facile strategy to produce bracelet cyclotides, leading to a general method to easily access their atomic resolution structures and providing a basis for development of biotechnological applications. Enabling Efficient Folding and High-Resolution Crystallographic Analysis of Bracelet Cyclotides.,Huang YH, Du Q, Jiang Z, King GJ, Collins BM, Wang CK, Craik DJ Molecules. 2021 Sep 13;26(18):5554. doi: 10.3390/molecules26185554. PMID:34577034[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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