TRNA(His) Guanylyltransferase (THG1), a Unique 3'-5' Nucleotidyl Transferase, Shares Unexpected Structural Homology with Canonical 5'-3' DNA Polymerases

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2010 Nov 10

PMID 21059936

Citations 41

Authors

Samantha J Hyde

Brian E Eckenroth

Brian A Smith

William A Eberley

Nicholas H Heintz

Jane E Jackman

Sylvie Doublie

Affiliations

Soon will be listed here.

Abstract

All known DNA and RNA polymerases catalyze the formation of phosphodiester bonds in a 5' to 3' direction, suggesting this property is a fundamental feature of maintaining and dispersing genetic information. The tRNA(His) guanylyltransferase (Thg1) is a member of a unique enzyme family whose members catalyze an unprecedented reaction in biology: 3'-5' addition of nucleotides to nucleic acid substrates. The 2.3-Å crystal structure of human THG1 (hTHG1) reported here shows that, despite the lack of sequence similarity, hTHG1 shares unexpected structural homology with canonical 5'-3' DNA polymerases and adenylyl/guanylyl cyclases, two enzyme families known to use a two-metal-ion mechanism for catalysis. The ability of the same structural architecture to catalyze both 5'-3' and 3'-5' reactions raises important questions concerning selection of the 5'-3' mechanism during the evolution of nucleotide polymerases.

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