6AC9

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

Summary for 6AC9

• Entry DOI: 10.2210/pdb6ac9/pdb
• Descriptor: Serine/threonine-protein kinase VRK1, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (8 entities in total)
• Functional Keywords: kinase, vaccinia-related kinase, vrk1, adenosine triphosphate, atp, amp-pnp, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 171417.02

Authors

Ngow, Y.S.,Sreekanth, R.,Yoon, H.S. (deposition date: 2018-07-25, release date: 2018-12-26, Last modification date: 2024-03-27)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.07 Å)