3WC2: Crystal structure of C. albicans tRNA(His) guanylyltransferase (Thg1) with a tRNA(Phe)(GUG)

Nucleotide polymerization proceeds in the forward (5'-3') direction. This tenet of the central dogma of molecular biology is found in diverse processes including transcription, reverse transcription, DNA replication, and even in lagging strand synthesis where reverse polymerization (3'-5') would present a "simpler" solution. Interestingly, reverse (3'-5') nucleotide addition is catalyzed by the tRNA maturation enzyme tRNA(His) guanylyltransferase, a structural homolog of canonical forward polymerases. We present a Candida albicans tRNA(His) guanylyltransferase-tRNA(His) complex structure that reveals the structural basis of reverse polymerization. The directionality of nucleotide polymerization is determined by the orientation of approach of the nucleotide substrate. The tRNA substrate enters the enzyme's active site from the opposite direction (180 degrees flip) compared with similar nucleotide substrates of canonical 5'-3' polymerases, and the finger domains are on opposing sides of the core palm domain. Structural, biochemical, and phylogenetic data indicate that reverse polymerization appeared early in evolution and resembles a mirror image of the forward process.
PDB ID: 3WC2Download
MMDB ID: 115992
PDB Deposition Date: 2013/5/24
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 3.641  Å
Source Organism:
Candida albicans SC5314
Similar Structures:
Biological Unit for 3WC2: hexameric; determined by author and by software (PISA)
Molecular Components in 3WC2
Label Count Molecule
Proteins (4 molecules)
Likely Histidyl tRNA-specific Guanylyltransferase
Molecule annotation
Nucleotide(1 molecule)
Molecule annotation
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