Structure of TYW1 with a lysine-pyruvate adduct boundStructure of TYW1 with a lysine-pyruvate adduct bound

Structural highlights

6djt is a 1 chain structure with sequence from Methanocaldococcus jannaschii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.64Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TYW1_METJA Component of the wyosine derivatives biosynthesis pathway that catalyzes the condensation of N-methylguanine with 2 carbon atoms from pyruvate to form the tricyclic 4-demethylwyosine (imG-14) on guanosine-37 of tRNA(Phe).[HAMAP-Rule:MF_01921][1]

Publication Abstract from PubMed

TYW1 is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the condensation of pyruvate and N-methylguanosine to form the posttranscriptional modification, 4-demethylwyosine, in situ on transfer RNA (tRNA). Two mechanisms have been proposed for this transformation, with one of the possible mechanisms invoking a Schiff base intermediate formed between a conserved lysine residue and pyruvate. Utilizing a combination of mass spectrometry and X-ray crystallography, we have obtained evidence to support the formation of a Schiff base lysine adduct in TYW1. When (13)C labeled pyruvate is used, the mass shift of the adduct matches that of the labeled pyruvate, indicating that pyruvate is the source of the adduct. Furthermore, a crystal structure of TYW1 provides visualization of the Schiff base lysine-pyruvate adduct, which is positioned directly adjacent to the auxiliary [4Fe-4S] cluster. The adduct coordinates the unique iron of the auxiliary cluster through the lysine nitrogen and a carboxylate oxygen, reminiscent of how the radical SAM [4Fe-4S] cluster is coordinated by SAM. The structure provides insight into the binding site for tRNA and further suggests how radical SAM chemistry can be combined with Schiff base chemistry for RNA modification.

Biochemical and Structural Characterization of a Schiff Base in the Radical-Mediated Biosynthesis of 4-Demethylwyosine by TYW1.,Grell TAJ, Young AP, Drennan CL, Bandarian V J Am Chem Soc. 2018 Jun 6;140(22):6842-6852. doi: 10.1021/jacs.8b01493. Epub 2018, May 24. PMID:29792696[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Young AP, Bandarian V. Pyruvate is the source of the two carbons that are required for formation of the imidazoline ring of 4-demethylwyosine. Biochemistry. 2011 Dec 13;50(49):10573-5. doi: 10.1021/bi2015053. Epub 2011 Nov, 14. PMID:22026549 doi:http://dx.doi.org/10.1021/bi2015053
  2. Grell TAJ, Young AP, Drennan CL, Bandarian V. Biochemical and Structural Characterization of a Schiff Base in the Radical-Mediated Biosynthesis of 4-Demethylwyosine by TYW1. J Am Chem Soc. 2018 Jun 6;140(22):6842-6852. doi: 10.1021/jacs.8b01493. Epub 2018, May 24. PMID:29792696 doi:http://dx.doi.org/10.1021/jacs.8b01493

6djt, resolution 1.64Å

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