This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1nop
From Proteopedia
Crystal structure of human tyrosyl-DNA phosphodiesterase (Tdp1) in complex with vanadate, DNA and a human topoisomerase I-derived peptide
Overview
Tyrosyl-DNA phosphodiesterase (Tdp1) is a member of the phospholipase D superfamily and acts as a DNA repair enzyme that removes stalled topoisomerase I- DNA complexes by hydrolyzing the bond between a tyrosine side chain and a DNA 3' phosphate. Despite the complexity of the substrate of this phosphodiesterase, vanadate succeeded in linking human Tdp1, a tyrosine-containing peptide, and a single-stranded DNA oligonucleotide into a quaternary complex that mimics the transition state for the first step of the catalytic reaction. The conformation of the bound substrate mimic gives compelling evidence that the topoisomerase I-DNA complex must undergo extensive modification prior to cleavage by Tdp1. The structure also illustrates that the use of vanadate as the central moiety in high-order complexes has the potential to be a general method for capturing protein-substrate interactions for phosphoryl transfer enzymes, even when the substrates are large, complicated, and unusual.
About this Structure
1NOP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of a transition state mimic for Tdp1 assembled from vanadate, DNA, and a topoisomerase I-derived peptide., Davies DR, Interthal H, Champoux JJ, Hol WG, Chem Biol. 2003 Feb;10(2):139-47. PMID:12618186 Page seeded by OCA on Sat May 3 02:47:22 2008
