6YHR

Crystal structure of Werner syndrome helicase

6YHR の概要

• エントリーDOI: 10.2210/pdb6yhr/pdb
• 分子名称: Werner syndrome ATP-dependent helicase, ADENOSINE-5'-DIPHOSPHATE, ZINC ION, ... (4 entities in total)
• 機能のキーワード: helicase, werners syndrome, dna repair, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 67413.75

構造登録者

Newman, J.A.,Gavard, A.E.,Savitsky, P.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.,Bountra, C.,Gileadi, O. (登録日: 2020-03-30, 公開日: 2020-04-29, 最終更新日: 2024-10-16)

主引用文献

Newman, J.A.,Gavard, A.E.,Lieb, S.,Ravichandran, M.C.,Hauer, K.,Werni, P.,Geist, L.,Bottcher, J.,Engen, J.R.,Rumpel, K.,Samwer, M.,Petronczki, M.,Gileadi, O.
Structure of the helicase core of Werner helicase, a key target in microsatellite instability cancers.
Life Sci Alliance, 4:-, 2021

PubMed Abstract: Loss of WRN, a DNA repair helicase, was identified as a strong vulnerability of microsatellite instable (MSI) cancers, making WRN a promising drug target. We show that ATP binding and hydrolysis are required for genome integrity and viability of MSI cancer cells. We report a 2.2-Å crystal structure of the WRN helicase core (517-1,093), comprising the two helicase subdomains and winged helix domain but not the HRDC domain or nuclease domains. The structure highlights unusual features. First, an atypical mode of nucleotide binding that results in unusual relative positioning of the two helicase subdomains. Second, an additional β-hairpin in the second helicase subdomain and an unusual helical hairpin in the Zn binding domain. Modelling of the WRN helicase in complex with DNA suggests roles for these features in the binding of alternative DNA structures. NMR analysis shows a weak interaction between the HRDC domain and the helicase core, indicating a possible biological role for this association. Together, this study will facilitate the structure-based development of inhibitors against WRN helicase.

PubMed: 33199508
DOI: 10.26508/lsa.202000795

実験手法

X-RAY DIFFRACTION (2.2 Å)