9PCQ

Phosphorylation of a Conserved Aspartate at the Eukaryotic Elongation Factor 2 Kinase Catalytic Site

This is a non-PDB format compatible entry.

Summary for 9PCQ

• Entry DOI: 10.2210/pdb9pcq/pdb
• Descriptor: Eukaryotic elongation factor 2 kinase, Calmodulin-1, ADENOSINE-5'-DIPHOSPHATE, ... (7 entities in total)
• Functional Keywords: eef2k, kinase, calmodulin, elongation, translation
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 78220.82

Authors

Piserchio, A.,Isiorho, E.A.,Dalby, K.,Ghose, R. (deposition date: 2025-06-28, release date: 2026-03-04)

Primary citation

Piserchio, A.,Isiorho, E.A.,Abzalimov, R.,Dalby, K.N.,Ghose, R.
Phosphorylation of a conserved aspartate in the catalytic site of eukaryotic elongation factor 2 kinase.
Protein Sci., 35:e70442-e70442, 2026

PubMed Abstract: Eukaryotic elongation factor 2 kinase (eEF-2K) is a member of the α-kinase family of atypical serine/threonine kinases. eEF-2K, the only calmodulin-activated α-kinase, phosphorylates the ribosome-associated GTPase, eukaryotic elongation factor 2 (eEF-2), suppressing translational elongation. α-kinases, including eEF-2K, possess catalytic site geometries that are distinct from those of typical kinases, suggesting possible divergence in their phospho-transfer mechanisms. Unlike typical protein kinases, where chemistry is known to proceed through a sequential mechanism involving a ternary kinase-substrate-ATP•Mg complex, the nature of the chemical step catalyzed by α-kinases remains poorly defined. Here, multiple orthogonal lines of evidence, including a crystal structure and solution-state mass spectrometry data, suggest phosphorylation of a catalytically essential aspartate residue (D284) at the eEF-2K active site. Previous crystallographic evidence of the presence of a phospho-aspartate at an equivalent position (D766) in the related Dictyostelium α-kinase MHCK-A strongly suggests that this species represents a conserved active-site feature in α-kinase family members, despite their disparate modes of activation. This observation, together with existing kinetics data on eEF-2K, raises the possibility that phospho-transfer chemistry in α-kinases occurs via an ordered stepwise mechanism involving a phospho-enzyme intermediate, contrasting with typical protein kinases.

PubMed: 41432361
DOI: 10.1002/pro.70442

Experimental method

X-RAY DIFFRACTION (2.3 Å)