4eyj | pdb_00004eyj

MAPK13 Complex with inhibitor

spinqualitylabelsall models 4eyj, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4eyj is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: N61 Related: 4exu, 4eym Gene: MAPK13, PRKM13, SAPK4 (Homo sapiens) Activity: Mitogen-activated protein kinase, with EC number 2.7.11.24 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Increased mucus production is a common cause of morbidity and mortality in inflammatory airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the precise molecular mechanisms for pathogenic mucus production are largely undetermined. Accordingly, there are no specific and effective anti-mucus therapeutics. Here, we define a signaling pathway from chloride channel calcium-activated 1 (CLCA1) to MAPK13 that is responsible for IL-13-driven mucus production in human airway epithelial cells. The same pathway was also highly activated in the lungs of humans with excess mucus production due to COPD. We further validated the pathway by using structure-based drug design to develop a series of novel MAPK13 inhibitors with nanomolar potency that effectively reduced mucus production in human airway epithelial cells. These results uncover and validate a new pathway for regulating mucus production as well as a corresponding therapeutic approach to mucus overproduction in inflammatory airway diseases. IL-13-induced airway mucus production is attenuated by MAPK13 inhibition.,Alevy YG, Patel AC, Romero AG, Patel DA, Tucker J, Roswit WT, Miller CA, Heier RF, Byers DE, Brett TJ, Holtzman MJ J Clin Invest. 2012 Dec 3;122(12):4555-68. doi: 10.1172/JCI64896. Epub 2012 Nov, 26. PMID:23187130 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Mitogen-activated protein kinase

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