4YCO

E. coli dihydrouridine synthase C (DusC) in complex with tRNAPhe

Summary for 4YCO

• Entry DOI: 10.2210/pdb4yco/pdb
• Related: 4BF9 4BFA
• Descriptor: tRNA-dihydrouridine synthase C, tRNAphe, FLAVIN MONONUCLEOTIDE, ... (6 entities in total)
• Functional Keywords: trna modification, oxidoreductase
• Biological source: Escherichia coli (strain K12); More
• Total number of polymer chains: 6
• Total formula weight: 182938.06

Authors

Byrne, R.T.,Jenkins, H.T.,Peters, D.T.,Whelan, F.,Stowell, J.,Aziz, N.,Kasatsky, P.,Rodnina, M.V.,Koonin, E.V.,Konevega, A.L.,Antson, A.A. (deposition date: 2015-02-20, release date: 2015-04-22, Last modification date: 2024-01-10)

Primary citation

Byrne, R.T.,Jenkins, H.T.,Peters, D.T.,Whelan, F.,Stowell, J.,Aziz, N.,Kasatsky, P.,Rodnina, M.V.,Koonin, E.V.,Konevega, A.L.,Antson, A.A.
Major reorientation of tRNA substrates defines specificity of dihydrouridine synthases.
Proc.Natl.Acad.Sci.USA, 112:6033-6037, 2015

PubMed Abstract: The reduction of specific uridines to dihydrouridine is one of the most common modifications in tRNA. Increased levels of the dihydrouridine modification are associated with cancer. Dihydrouridine synthases (Dus) from different subfamilies selectively reduce distinct uridines, located at spatially unique positions of folded tRNA, into dihydrouridine. Because the catalytic center of all Dus enzymes is conserved, it is unclear how the same protein fold can be reprogrammed to ensure that nucleotides exposed at spatially distinct faces of tRNA can be accommodated in the same active site. We show that the Escherichia coli DusC is specific toward U16 of tRNA. Unexpectedly, crystal structures of DusC complexes with tRNA(Phe) and tRNA(Trp) show that Dus subfamilies that selectively modify U16 or U20 in tRNA adopt identical folds but bind their respective tRNA substrates in an almost reverse orientation that differs by a 160° rotation. The tRNA docking orientation appears to be guided by subfamily-specific clusters of amino acids ("binding signatures") together with differences in the shape of the positively charged tRNA-binding surfaces. tRNA orientations are further constrained by positional differences between the C-terminal "recognition" domains. The exquisite substrate specificity of Dus enzymes is therefore controlled by a relatively simple mechanism involving major reorientation of the whole tRNA molecule. Such reprogramming of the enzymatic specificity appears to be a unique evolutionary solution for altering tRNA recognition by the same protein fold.

PubMed: 25902496
DOI: 10.1073/pnas.1500161112

Experimental method

X-RAY DIFFRACTION (2.1 Å)