PDBsum entry 4eyj

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Transferase/transferase inhibitor PDB id
Protein chain
338 a.a.
Waters ×276
PDB id:
Name: Transferase/transferase inhibitor
Title: Mapk13 complex with inhibitor
Structure: Mitogen-activated protein kinase 13. Chain: a. Fragment: unp residues 1-352. Synonym: map kinase 13, mapk 13, mitogen-activated protein delta, map kinase p38 delta, stress-activated protein kinas engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk13, prkm13, sapk4. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.10Å     R-factor:   0.244     R-free:   0.275
Authors: C.A.Miller,T.J.Brett
Key ref: Y.G.Alevy et al. (2012). IL-13-induced airway mucus production is attenuated by MAPK13 inhibition. J Clin Invest, 122, 4555-4568. PubMed id: 23187130 DOI: 10.1172/JCI64896
01-May-12     Release date:   19-Dec-12    
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Protein chain
Pfam   ArchSchema ?
O15264  (MK13_HUMAN) -  Mitogen-activated protein kinase 13
365 a.a.
338 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Mitogen-activated protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytosol   1 term 
  Biological process     intracellular signal transduction   14 terms 
  Biochemical function     nucleotide binding     9 terms  


DOI no: 10.1172/JCI64896 J Clin Invest 122:4555-4568 (2012)
PubMed id: 23187130  
IL-13-induced airway mucus production is attenuated by MAPK13 inhibition.
Y.G.Alevy, A.C.Patel, A.G.Romero, D.A.Patel, J.Tucker, W.T.Roswit, C.A.Miller, R.F.Heier, D.E.Byers, T.J.Brett, M.J.Holtzman.
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.