3AY0

Crystal structure of Methanocaldococcus jannaschii Trm5 in complex with adenosine

Summary for 3AY0

• Entry DOI: 10.2210/pdb3ay0/pdb
• Related: 3AXZ
• Descriptor: Uncharacterized protein MJ0883, ZINC ION, ADENOSINE, ... (4 entities in total)
• Functional Keywords: rossmann fold, methyltransferase, adomet binding, transferase
• Biological source: Methanocaldococcus jannaschii
• Cellular location: Cytoplasm (Potential): Q58293
• Total number of polymer chains: 2
• Total formula weight: 79005.43

Authors

Goto-Ito, S.,Ito, T.,Hou, Y.M.,Yokoyama, S. (deposition date: 2011-04-21, release date: 2011-08-17, Last modification date: 2024-10-30)

Primary citation

Lahoud, G.,Goto-Ito, S.,Yoshida, K.,Ito, T.,Yokoyama, S.,Hou, Y.M.
Differentiating analogous tRNA methyltransferases by fragments of the methyl donor.
Rna, 17:1236-1246, 2011

PubMed Abstract: Bacterial TrmD and eukaryotic-archaeal Trm5 form a pair of analogous tRNA methyltransferase that catalyze methyl transfer from S-adenosyl methionine (AdoMet) to N(1) of G37, using catalytic motifs that share no sequence or structural homology. Here we show that natural and synthetic analogs of AdoMet are unable to distinguish TrmD from Trm5. Instead, fragments of AdoMet, adenosine and methionine, are selectively inhibitory of TrmD rather than Trm5. Detailed structural information of the two enzymes in complex with adenosine reveals how Trm5 escapes targeting by adopting an altered structure, whereas TrmD is trapped by targeting due to its rigid structure that stably accommodates the fragment. Free energy analysis exposes energetic disparities between the two enzymes in how they approach the binding of AdoMet versus fragments and provides insights into the design of inhibitors selective for TrmD.

PubMed: 21602303
DOI: 10.1261/rna.2706011

Experimental method

X-RAY DIFFRACTION (3.05 Å)