3D2G

Structural basis of thiamine pyrophosphate analogues binding to the eukaryotic riboswitch

Summary for 3D2G

• Entry DOI: 10.2210/pdb3d2g/pdb
• Related: 2cky 3D2V 3D2X
• Descriptor: TPP-specific riboswitch, MAGNESIUM ION, THIAMINE DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: rna, riboswitch, tpp, thiamine analogues, antibiotics, arabidopsis thaliana, eukaryote
• Biological source: Arabidopsis thaliana
• Total number of polymer chains: 2
• Total formula weight: 51011.35

Authors

Thore, S. (deposition date: 2008-05-08, release date: 2008-07-01, Last modification date: 2023-08-30)

Primary citation

Thore, S.,Frick, C.,Ban, N.
Structural basis of thiamine pyrophosphate analogues binding to the eukaryotic riboswitch
J.Am.Chem.Soc., 130:8116-8117, 2008

PubMed Abstract: The thiamine pyrophosphate (TPP)-sensing riboswitch is the only riboswitch found in eukaryotes. In plants, TPP regulates its own production by binding to the 3' untranslated region of the mRNA encoding ThiC, a critical enzyme in thiamine biosynthesis, which promotes the formation of an unstable splicing variant. In order to better understand the molecular basis of TPP-analogue binding to the eukaryotic TPP-responsive riboswitch, we have determined the crystal structures of the Arabidopsis thaliana TPP-riboswitch in complex with oxythiamine pyrophosphate (OTPP) and with the antimicrobial compound pyrithiamine pyrophosphate (PTPP). The OTPP-riboswitch complex reveals that the pyrimidine ring of OTPP is stabilized in its enol form in order to retain key interactions with guanosine 28 of the riboswitch previously observed in the TPP complex. The structure of PTPP in complex with the riboswitch shows that the base moiety of guanosine 60 undergoes a conformational change to cradle the pyridine ring of the PTPP. Structural information from these complexes has implications for the design of novel antimicrobials targeting TPP-sensing riboswitches.

PubMed: 18533652
DOI: 10.1021/ja801708e

Experimental method

X-RAY DIFFRACTION (2.25 Å)