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4YNO

Crystal structure of MAPK13 at INACTIVE FORM

Replaces:  4EXU
Summary for 4YNO
Entry DOI10.2210/pdb4yno/pdb
Related4eyj 4eym 4myg
DescriptorMitogen-activated protein kinase 13 (2 entities in total)
Functional Keywordsp38 kinase, transferase
Biological sourceHomo sapiens (Human)
Total number of polymer chains1
Total formula weight42633.90
Authors
Miller, C.A.,Brett, T.J. (deposition date: 2015-03-10, release date: 2015-04-08, Last modification date: 2023-09-27)
Primary citationAlevy, Y.G.,Patel, A.C.,Romero, A.G.,Patel, D.A.,Tucker, J.,Roswit, W.T.,Miller, C.A.,Heier, R.F.,Byers, D.E.,Brett, T.J.,Holtzman, M.J.
IL-13-induced airway mucus production is attenuated by MAPK13 inhibition.
J.Clin.Invest., 122:4555-4568, 2012
Cited by
PubMed Abstract: 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.
PubMed: 23187130
DOI: 10.1172/JCI64896
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.7 Å)
Structure validation

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