[4Fe-4S]-dependent enzymes in non-redox tRNA thiolation.

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Post-transcriptional modification of nucleosides in transfer RNAs (tRNAs) is essential for accurate protein synthesis.
• Sulfur-containing nucleosides like 2-thiouridine (s²U) and 2-methylthioadenosine (ms²A) are vital modifications within tRNAs.
• While persulfide chemistry was the long-standing model, [4Fe-4S] clusters are now recognized in many tRNA thiolation enzymes.

Purpose of the Study:

• To review recent advancements in understanding [4Fe-4S]-dependent tRNA thiolation enzymes.
• To summarize biochemical, spectroscopic, and structural data on these enzymes.
• To highlight the shift from persulfide chemistry to [4Fe-4S] cluster involvement in tRNA thiolation.

Main Methods:

• Biochemical characterization of tRNA thiolation enzymes.
• Spectroscopic analyses to study enzyme mechanisms and structures.
• X-ray crystallography and other structural biology techniques to determine enzyme structures.

Main Results:

• Multiple tRNA thiolation enzymes utilize [4Fe-4S] clusters for their catalytic activity.
• Detailed biochemical and structural data reveal the mechanisms of these novel enzymes.
• The role of [4Fe-4S] clusters in non-redox tRNA thiolation is elucidated.

Conclusions:

• [4Fe-4S] clusters are a key feature of many tRNA thiolation enzymes, representing a significant departure from previous models.
• Understanding these enzymes is crucial for comprehending the fidelity of translation.
• This review consolidates a decade of research on these important biological catalysts.