3ALN

Crystal Structure of human non-phosphorylated MKK4 kinase domain complexed with AMP-PNP

Summary for 3ALN

• Entry DOI: 10.2210/pdb3aln/pdb
• Related: 3ALO
• Descriptor: Dual specificity mitogen-activated protein kinase kinase 4, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION (3 entities in total)
• Functional Keywords: kinase, protein amp-pnp complex, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P45985
• Total number of polymer chains: 3
• Total formula weight: 113980.19

Authors

Matsumoto, T.,Kinoshita, T.,Kirii, Y.,Yokota, K.,Hamada, K.,Tada, T. (deposition date: 2010-08-04, release date: 2010-10-27, Last modification date: 2023-11-01)

Primary citation

Matsumoto, T.,Kinoshita, T.,Kirii, Y.,Yokota, K.,Hamada, K.,Tada, T.
Crystal structures of MKK4 kinase domain reveal that substrate peptide binds to an allosteric site and induces an auto-inhibition state
Biochem.Biophys.Res.Commun., 400:369-373, 2010

PubMed Abstract: MKK4 activates both JNKs and p38s. We determined the crystal structures of human non-phosphorylated MKK4 kinase domain (npMKK4) complexed with AMP-PNP (npMKK4/AMP) and a ternary complex of npMKK4, AMP-PNP and p38α peptide (npMKK4/AMP/p38). These crystal structures revealed that the p38α peptide-bound npMKK4 at the allosteric site rather than at the putative substrate binding site and induced an auto-inhibition state. While the activation loop of the npMKK4/AMP complex was disordered, in the npMKK4/AMP/p38 complex it configured a long α-helix, which prevented substrate access to the active site and αC-helix movement to the active configuration of MKK4.

PubMed: 20732303
DOI: 10.1016/j.bbrc.2010.08.071

Experimental method

X-RAY DIFFRACTION (2.3 Å)