6AC9

Crystal structure of human Vaccinia-related kinase 1 (VRK1) in complex with AMP-PNP

6AC9 の概要

• エントリーDOI: 10.2210/pdb6ac9/pdb
• 分子名称: Serine/threonine-protein kinase VRK1, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (8 entities in total)
• 機能のキーワード: kinase, vaccinia-related kinase, vrk1, adenosine triphosphate, atp, amp-pnp, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 171417.02

構造登録者

Ngow, Y.S.,Sreekanth, R.,Yoon, H.S. (登録日: 2018-07-25, 公開日: 2018-12-26, 最終更新日: 2024-03-27)

主引用文献

Ngow, Y.S.,Rajan, S.,Ye, H.,Yoon, H.S.
Crystal structure of human vaccinia-related kinase 1 in complex with AMP-PNP, a non-hydrolyzable ATP analog.
Protein Sci., 28:524-532, 2019

PubMed Abstract: Vaccinia-related kinase 1 (VRK1), a serine/threonine mitotic kinase, is widely over-expressed in dividing cells and regarded as a cancer drug target primarily due to its function as an early response gene in cell proliferation. However, the mechanism of VRK1 phosphorylation and substrate activation is not well understood. More importantly even the molecular basis of VRK1 interaction with its cofactor, adenosine triphosphate (ATP), is unavailable to-date. As designing specific inhibitors remains to be the major challenge in kinase research, such a molecular understanding will enable us to design ATP-competitive specific inhibitors of VRK1. Here we report the molecular characterization of VRK1 in complex with AMP-PNP, a non-hydrolyzable ATP-analog, using NMR titration followed by the co-crystal structure determined upto 2.07 Å resolution. We also carried out the structural comparison of the AMP-PNP bound-form with its apo and inhibitor-bound counterparts, which has enabled us to present our rationale toward designing VRK1-specific inhibitors.

PubMed: 30461091
DOI: 10.1002/pro.3552

実験手法

X-RAY DIFFRACTION (2.07 Å)