PDBsum entry 1r3c

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protein metals links
Transferase PDB id
Protein chain
349 a.a. *
_MG ×2
Waters ×268
* Residue conservation analysis
PDB id:
Name: Transferase
Title: The structure of p38alpha c162s mutant
Structure: Mitogen-activated protein kinase 14. Chain: a. Synonym: mitogen-activated protein kinase p38alpha, map kinase p38alpha, cytokine suppressive anti-inflammatory drug binding protein, csaid binding protein, csbp, max- interacting protein 2, map kinase mxi2, sapk2a. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk14. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
2.00Å     R-factor:   0.200     R-free:   0.224
Authors: S.B.Patel,P.M.Cameron,B.Frantz-Wattley,E.O'Neill,J.W.Becker, G.Scapin
Key ref: S.B.Patel et al. (2004). Lattice stabilization and enhanced diffraction in human p38 alpha crystals by protein engineering. Biochim Biophys Acta, 1696, 67-73. PubMed id: 14726206
01-Oct-03     Release date:   20-Jan-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q16539  (MK14_HUMAN) -  Mitogen-activated protein kinase 14
360 a.a.
349 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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     cell   8 terms 
  Biological process     intracellular signal transduction   71 terms 
  Biochemical function     nucleotide binding     11 terms  


Biochim Biophys Acta 1696:67-73 (2004)
PubMed id: 14726206  
Lattice stabilization and enhanced diffraction in human p38 alpha crystals by protein engineering.
S.B.Patel, P.M.Cameron, B.Frantz-Wattley, E.O'Neill, J.W.Becker, G.Scapin.
Mitogen-activated protein (MAP) kinase p38 alpha is activated in response to environmental stress and cytokines, and plays a significant role in inflammatory responses. For these reasons, it is an important target for the treatment of a wide range of inflammatory and autoimmune diseases. The crystals of p38 alpha that we obtained by published procedures were usually small, quite mosaic, and difficult to reproduce and thus posed a difficulty for the intensive high-resolution studies required for a structure-guided drug discovery approach. Based on crystallographic and biochemical evidences, we prepared a single point mutation of a surface cysteine (C162S) and found that it prevents aggregation and improves the homogeneity and stability of the enzyme. This mutation also facilitates the crystallization process and increases the diffracting power of p38 alpha crystals. Surprisingly, we found that the mutation induces a change in the conformation of a nearby surface loop resulting in stronger lattice interactions, consistent with the improved crystal quality. The mutant protein, because of its improved stability and strengthened lattice interactions, thus provides a significantly improved reagent for use in structure-based drug design for this important disease target.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20445236 Z.S.Derewenda (2010).
Application of protein engineering to enhance crystallizability and improve crystal properties.
  Acta Crystallogr D Biol Crystallogr, 66, 604-615.  
19622861 S.B.Patel, P.M.Cameron, S.J.O'Keefe, B.Frantz-Wattley, J.Thompson, E.A.O'Neill, T.Tennis, L.Liu, J.W.Becker, and G.Scapin (2009).
The three-dimensional structure of MAP kinase p38beta: different features of the ATP-binding site in p38beta compared with p38alpha.
  Acta Crystallogr D Biol Crystallogr, 65, 777-785.
PDB codes: 3gc7 3gc8 3gc9
17694525 D.Kuhn, N.Weskamp, E.Hüllermeier, and G.Klebe (2007).
Functional Classification of Protein Kinase Binding Sites Using Cavbase.
  ChemMedChem, 2, 1432-1447.  
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