Publication Abstract from PubMed
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 A resolution and represents an auto-inhibition state of MAP2K6. Three characteristics of short alpha-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 alphaC-helix, a component essential for forming the active configuration, away from the active site. AH1 and AH2 were found to enclose the gamma-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.
Crystal structure of non-phosphorylated MAP2K6 in a putative auto-inhibition state.,Matsumoto T, Kinoshita T, Matsuzaka H, Nakai R, Kirii Y, Yokota K, Tada T J Biochem. 2012 May;151(5):541-9. Epub 2012 Mar 1. PMID:22383536[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
