5E4H

Crystal Structure of Apoenzyme Alpha-kinase Domain of Myosin-II Heavy Chain Kinase A

Summary for 5E4H

• Entry DOI: 10.2210/pdb5e4h/pdb
• Related: 3LKM 3LLA 3LMH 3LMI 3PDT 4ZME 4ZMF 4ZS4 5E9E
• Descriptor: Myosin-II heavy chain kinase A, ZINC ION (3 entities in total)
• Functional Keywords: alpha kinase, epk domain fold, transferase
• Biological source: Dictyostelium discoideum (Slime mold)
• Total number of polymer chains: 8
• Total formula weight: 278015.58

Authors

Ye, Q.,Cote, G.P.,Jia, Z. (deposition date: 2015-10-06, release date: 2016-06-08, Last modification date: 2023-09-27)

Primary citation

Ye, Q.,Yang, Y.,van Staalduinen, L.,Crawley, S.W.,Liu, L.,Brennan, S.,Cote, G.P.,Jia, Z.
Structure of the Dictyostelium Myosin-II Heavy Chain Kinase A (MHCK-A) alpha-kinase domain apoenzyme reveals a novel autoinhibited conformation.
Sci Rep, 6:26634-26634, 2016

PubMed Abstract: The α-kinases are a family of a typical protein kinases present in organisms ranging from protozoa to mammals. Here we report an autoinhibited conformation for the α-kinase domain of Dictyostelium myosin-II heavy chain kinase A (MHCK-A) in which nucleotide binding to the catalytic cleft, located at the interface between an N-terminal and C-terminal lobe, is sterically blocked by the side chain of a conserved arginine residue (Arg592). Previous α-kinase structures have shown that an invariant catalytic aspartic acid residue (Asp766) is phosphorylated. Unexpectedly, in the autoinhibited conformation the phosphoryl group is transferred to the adjacent Asp663, creating an interaction network that stabilizes the autoinhibited state. The results suggest that Asp766 phosphorylation may play both catalytic and regulatory roles. The autoinhibited structure also provides the first view of a phosphothreonine residue docked into the phospho-specific allosteric binding site (Pi-pocket) in the C-lobe of the α-kinase domain.

PubMed: 27211275
DOI: 10.1038/srep26634

Experimental method

X-RAY DIFFRACTION (2.9 Å)