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Publication Abstract from PubMed

Alpha-momorcharin (Alpha-MMC) from the seed of bitter melon is a type I ribosome inactivating protein (RIP) that removes a specific adenine from 28S rRNA and inhibits protein biosynthesis. Here, we report seven crystal complex structures of alpha-MMC with different substrate analogs (adenine, AMP, cAMP, dAMP, ADP, GMP, and xanthosine) at 1.08 A to 1.52 A resolution. These structures reveal that not only adenine, but also guanine and their analogs can effectively bind to alpha-MMC. The side chain of Tyr93 adopts two conformations, serving as a switch to open and close the substrate binding pocket of alpha-MMC. Although adenine, AMP, GMP, and guanine are located in a similar active site in different RIPs, residues involved in the interaction between RIPs and substrate analogs are slightly different. Complex structures of alpha-MMC with different substrate analogs solved in this study provide useful information on its enzymatic mechanisms and may enable the development of new inhibitors to treat the poisoning of alpha-MMC.

Atomic-resolution structures of type I ribosome inactivating protein alpha-momorcharin with different substrate analogs.,Fan X, Wang Y, Guo F, Zhang Y, Jin T Int J Biol Macromol. 2020 Dec 1;164:265-276. doi: 10.1016/j.ijbiomac.2020.07.063., Epub 2020 Jul 10. PMID:32653369^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.