Structural basis for recognition of 5′-phosphotyrosine adducts by TDP2

Structural basis for recognition of 5′-phosphotyrosine adducts by TDP2

The DNA repair enzyme TDP2 resolves 5′-phosphotyrosyl-DNA adducts, and is responsible for resistance to anti-cancer drugs that target covalent topoisomerase-DNA complexes. TDP2 also participates in key signaling pathways during development and tumorigenesis, and cleaves a protein-RNA linkage during...

Full description

Bibliographic Details
Main Authors: Shi, Ke, Kurahashi, Kayo, Gao, Rui, Tsutakawa, Susan E, Tainer, John A, Pommier, Yves, Aihara, Hideki
Format: Online
Language:English
Published: 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515695/
id pubmed-3515695
recordtype oai_dc
spelling pubmed-35156952013-06-01 Structural basis for recognition of 5′-phosphotyrosine adducts by TDP2 Shi, Ke Kurahashi, Kayo Gao, Rui Tsutakawa, Susan E Tainer, John A Pommier, Yves Aihara, Hideki Article The DNA repair enzyme TDP2 resolves 5′-phosphotyrosyl-DNA adducts, and is responsible for resistance to anti-cancer drugs that target covalent topoisomerase-DNA complexes. TDP2 also participates in key signaling pathways during development and tumorigenesis, and cleaves a protein-RNA linkage during picornavirus replication. The crystal structure of zebrafish TDP2 bound to DNA reveals a deep and narrow basic groove that selectively accommodates the 5′-end of single-stranded DNA in a stretched conformation. The crystal structure of the full-length C. elegans TDP2 shows that this groove can also accommodate an acidic peptide stretch in vitro, with Glu and Asp sidechains occupying the DNA backbone phosphate binding sites. This extensive molecular mimicry suggests a potential mechanism for auto-regulation and how TDP2 may interact with phosphorylated proteins in signaling. Our study provides a framework to interrogate functions of TDP2 and develop inhibitors for chemotherapeutic and antiviral applications. 2012-10-28 2012-12 /pmc/articles/PMC3515695/ /pubmed/23104058 http://dx.doi.org/10.1038/nsmb.2423 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Shi, Ke
Kurahashi, Kayo
Gao, Rui
Tsutakawa, Susan E
Tainer, John A
Pommier, Yves
Aihara, Hideki
spellingShingle Shi, Ke
Kurahashi, Kayo
Gao, Rui
Tsutakawa, Susan E
Tainer, John A
Pommier, Yves
Aihara, Hideki
Structural basis for recognition of 5′-phosphotyrosine adducts by TDP2
author_facet Shi, Ke
Kurahashi, Kayo
Gao, Rui
Tsutakawa, Susan E
Tainer, John A
Pommier, Yves
Aihara, Hideki
author_sort Shi, Ke
title Structural basis for recognition of 5′-phosphotyrosine adducts by TDP2
title_short Structural basis for recognition of 5′-phosphotyrosine adducts by TDP2
title_full Structural basis for recognition of 5′-phosphotyrosine adducts by TDP2
title_fullStr Structural basis for recognition of 5′-phosphotyrosine adducts by TDP2
title_full_unstemmed Structural basis for recognition of 5′-phosphotyrosine adducts by TDP2
title_sort structural basis for recognition of 5′-phosphotyrosine adducts by tdp2
description The DNA repair enzyme TDP2 resolves 5′-phosphotyrosyl-DNA adducts, and is responsible for resistance to anti-cancer drugs that target covalent topoisomerase-DNA complexes. TDP2 also participates in key signaling pathways during development and tumorigenesis, and cleaves a protein-RNA linkage during picornavirus replication. The crystal structure of zebrafish TDP2 bound to DNA reveals a deep and narrow basic groove that selectively accommodates the 5′-end of single-stranded DNA in a stretched conformation. The crystal structure of the full-length C. elegans TDP2 shows that this groove can also accommodate an acidic peptide stretch in vitro, with Glu and Asp sidechains occupying the DNA backbone phosphate binding sites. This extensive molecular mimicry suggests a potential mechanism for auto-regulation and how TDP2 may interact with phosphorylated proteins in signaling. Our study provides a framework to interrogate functions of TDP2 and develop inhibitors for chemotherapeutic and antiviral applications.
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515695/
_version_ 1611938507159240704

Similar Items