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Title: Global RNA Fold and Molecular Recognition for a pfl Riboswitch Bound to ZMP, a Master Regulator of One-Carbon Metabolism

ZTP, the pyrophosphorylated analog of ZMP (5- amino-4-imidazole carboxamide ribose-5'-monophosphate), was identified as an alarmone that senses 10-formyl-tetrahydroflate deficiency in bacteria. Recently, a pfl riboswitch was identified that selectively binds ZMP and regulates genes associated with purine biosynthesis and one-carbon metabolism. Here we report on the structure of the ZMP-bound Thermosinus carboxydivorans pfl riboswitch sensing domain, thereby defining the pseudoknot-based tertiary RNA fold, the binding-pocket architecture, and principles underlying ligand recognition specificity. Molecular recognition involves shape complementarity, with the ZMP 5-amino and carboxamide groups paired with the Watson-Crick edge of an invariant uracil, and the imidazole ring sandwiched between guanines, while the sugar hydroxyls form intermolecular hydrogen bond contacts. The burial of the ZMP base and ribose moieties, together with unanticipated coordination of the carboxamide by Mg2+, contrasts with exposure of the 5'-phosphate to solvent. Lastly, our studies highlight the principles underlying RNA-based recognition of ZMP, a master regulator of one-carbon metabolism.
Authors:
 [1] ;  [2] ;  [1]
  1. Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
  2. Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS); Cornell Univ., Argonne, IL (United States). Dept. of Chemistry and Chemical Biology
Publication Date:
OSTI Identifier:
1209696
Grant/Contract Number:
AC02-06CH11357; S10 RR029205; P41 GM103403
Type:
Accepted Manuscript
Journal Name:
Structure
Additional Journal Information:
Journal Volume: 23; Journal Issue: 8; Journal ID: ISSN 0969-2126
Publisher:
Elsevier
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org:
USDOE Office of Science (SC); National Institutes of Health (NIH)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY