5c0o | pdb_00005c0o
m1A58 tRNA methyltransferase mutant - Y78A
Structural highlights
FunctionTRMI_THET2 Catalyzes the S-adenosyl-L-methionine-dependent formation of N(1)-methyladenine at position 58 (m1A58) in tRNA. Is required for cell growth at extreme temperatures.[1] Publication Abstract from PubMedThe enzymes of the TrmI family catalyze the formation of the m1A58 modification in tRNA. We previously solved the crystal structure of the Thermus thermophilus enzyme and conducted a biophysical study to characterize the interaction between TrmI and tRNA. TrmI enzymes are active as a tetramer and up to two tRNAs can bind to TrmI simultaneously. In this paper, we present the structures of two TrmI mutants (D170A and Y78A). These residues are conserved in the active site of TrmIs and their mutations result in a dramatic alteration of TrmI activity. Both structures of TrmI mutants revealed the flexibility of the N-terminal domain that is probably important to bind tRNA. The structure of TrmI Y78A catalytic domain is unmodified regarding the binding of the SAM co-factor and the conformation of residues potentially interacting with the substrate adenine. This structure reinforces the previously proposed role of Y78, i.e. stabilize the conformation of the A58 ribose needed to hold the adenosine in the active site. The structure of the D170A mutant shows a flexible active site with one loop occupying in part the place of the co-factor and the second loop moving at the entrance to the active site. This structure and recent data confirms the central role of D170 residue binding the amino moiety of SAM and the exocyclic amino group of adenine. Possible mechanisms for methyl transfer are then discussed. The m1A modification in eubacterial tRNA: An overview of tRNA recognition and mechanism of catalysis by TrmI.,Degut C, Ponchon L, Folly-Klan M, Barraud P, Tisne C Biophys Chem. 2015 Jul 15. pii: S0301-4622(15)30017-X. doi:, 10.1016/j.bpc.2015.06.012. PMID:26189113[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
