3VN9

Rifined Crystal structure of non-phosphorylated MAP2K6 in a putative auto-inhibition state

Replaces:  3AN0

Summary for 3VN9

• Entry DOI: 10.2210/pdb3vn9/pdb
• Descriptor: Dual specificity mitogen-activated protein kinase kinase 6, 9-{5-O-[(R)-hydroxy{[(S)-hydroxy(phosphonoamino)phosphoryl]oxy}phosphoryl]-beta-L-ribofuranosyl}-9H-purin-6-amine, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: auto-inhibition state, activation helices, mitogen-activated protein kinase kinase, amp-pnp binding, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : P52564
• Total number of polymer chains: 1
• Total formula weight: 38899.70

Authors

Kinoshita, T.,Matsuzaka, H.,Nakai, R.,Kirii, Y.,Yokota, K.,Tada, T.,Matsumoto, T. (deposition date: 2012-01-05, release date: 2012-02-29, Last modification date: 2023-11-08)

Primary citation

Matsumoto, T.,Kinoshita, T.,Matsuzaka, H.,Nakai, R.,Kirii, Y.,Yokota, K.,Tada, T.
Crystal structure of non-phosphorylated MAP2K6 in a putative auto-inhibition state
J.Biochem., 151:541-549, 2012

PubMed Abstract: Mitogen-activated protein kinase kinase 6 (MAP2K6) plays a crucial role in the p38 MAP kinase signal cascade that regulates various stress-induced responses and is associated with pathological conditions. The crystal structure of human non-phosphorylated MAP2K6 (npMAP2K6) complexed with an ATP analogue was determined at 2.6 Å resolution and represents an auto-inhibition state of MAP2K6. Three characteristics of short α-helices configured in the activation loop region, termed activation helices (AH1, AH2 and AH3), are important in controlling the auto-inhibition mechanism. AH1 displaces the αC-helix, a component essential for forming the active configuration, away from the active site. AH1 and AH2 were found to enclose the γ-phosphate, the leaving group of ATP. A comparison with the related enzymes, MAP2K1 and MAP2K4 reveals that MAP2K6 has the unique auto-inhibition mechanism mediated by the three activation helices.

PubMed: 22383536
DOI: 10.1093/jb/mvs023

Experimental method

X-RAY DIFFRACTION (2.6 Å)