6LOQ

Atomic-resolution structures of type I ribosome inactivating protein alpha-momorcharin with different substrate analogs.

(2020) Int J Biol Macromol 164: 265-276

• PubMed: 32653369 Search on PubMed
• DOI: https://doi.org/10.1016/j.ijbiomac.2020.07.063
• Primary Citation of Related Structures:  
  6LOQ, 6LOR, 6LOV, 6LOW, 6LOY, 6LOZ, 6LP0


• PubMed Abstract: 
  

  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 Å to 1.52 Å 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.

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Organizational Affiliation: 

Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China; Laboratory of Structural Immunology, CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Molecular Cell Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.