4YNO

Crystal structure of MAPK13 at INACTIVE FORM

  • Classification: TRANSFERASE
  • Organism(s): Homo sapiens
  • Expression System: Escherichia coli
  • Mutation(s): No 

  • Deposited: 2015-03-10 Released: 2015-04-08 
  • Deposition Author(s): Miller, C.A., Brett, T.J.
  • Funding Organization(s): National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

IL-13-induced airway mucus production is attenuated by MAPK13 inhibition.

Alevy, 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.

(2012) J Clin Invest 122: 4555-4568

  • DOI: https://doi.org/10.1172/JCI64896
  • Primary Citation of Related Structures:  
    4EYJ, 4EYM, 4YNO

  • 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.


  • Organizational Affiliation

    Drug Discovery Program, Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Mitogen-activated protein kinase 13371Homo sapiensMutation(s): 0 
Gene Names: MAPK13PRKM13SAPK4
EC: 2.7.11.24
UniProt & NIH Common Fund Data Resources
Find proteins for O15264 (Homo sapiens)
Explore O15264 
Go to UniProtKB:  O15264
PHAROS:  O15264
GTEx:  ENSG00000156711 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO15264
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.923α = 90
b = 69.405β = 90
c = 92.506γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)United StatesP50-HL107183

Revision History  (Full details and data files)

  • Version 1.0: 2015-04-08
    Type: Initial release
  • Version 1.1: 2017-09-20
    Changes: Author supporting evidence, Database references, Derived calculations, Source and taxonomy
  • Version 1.2: 2019-12-04
    Changes: Author supporting evidence
  • Version 1.3: 2023-09-27
    Changes: Data collection, Database references, Refinement description