3VUL

Crystal structure of a cysteine-deficient mutant M1 in MAP kinase JNK1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.81 Å
  • R-Value Free: 0.315 
  • R-Value Work: 0.249 
  • R-Value Observed: 0.252 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Seven cysteine-deficient mutants depict the interplay between thermal and chemical stabilities of individual cysteine residues in mitogen-activated protein kinase c-Jun N-terminal kinase 1

Nakaniwa, T.Fukada, H.Inoue, T.Gouda, M.Nakai, R.Kirii, Y.Adachi, M.Tamada, T.Segawa, S.Kuroki, R.Tada, T.Kinoshita, T.

(2012) Biochemistry 51: 8410-8421

  • DOI: https://doi.org/10.1021/bi300918w
  • Primary Citation of Related Structures:  
    3VUD, 3VUG, 3VUH, 3VUI, 3VUK, 3VUL, 3VUM

  • PubMed Abstract: 

    Intracellular proteins can have free cysteines that may contribute to their structure, function, and stability; however, free cysteines can lead to chemical instabilities in solution because of oxidation-driven aggregation. The MAP kinase, c-Jun N-terminal kinase 1 (JNK1), possesses seven free cysteines and is an important drug target for autoimmune diseases, cancers, and apoptosis-related diseases. To characterize the role of cysteine residues in the structure, function, and stability of JNK1, we prepared and evaluated wild-type JNK1 and seven cysteine-deficient JNK1 proteins. The nonreduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis experiments showed that the chemical stability of JNK1 increased as the number of cysteines decreased. The contribution of each cysteine residue to biological function and thermal stability was highly susceptible to the environment surrounding the particular cysteine mutation. The mutations of solvent-exposed cysteine to serine did not influence biological function and increased the thermal stability. The mutation of the accessible cysteine involved in the hydrophobic pocket did not affect biological function, although a moderate thermal destabilization was observed. Cysteines in the loosely assembled hydrophobic environment moderately contributed to thermal stability, and the mutations of these cysteines had a negligible effect on enzyme activity. The other cysteines are involved in the tightly filled hydrophobic core, and mutation of these residues was found to correlate with thermal stability and enzyme activity. These findings about the role of cysteine residues should allow us to obtain a stable JNK1 and thus promote the discovery of potent JNK1 inhibitors.


  • Organizational Affiliation

    Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Mitogen-activated protein kinase 8370Homo sapiensMutation(s): 6 
EC: 2.7.11.24
UniProt & NIH Common Fund Data Resources
Find proteins for P45983 (Homo sapiens)
Explore P45983 
Go to UniProtKB:  P45983
PHAROS:  P45983
GTEx:  ENSG00000107643 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP45983
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Peptide from C-Jun-amino-terminal kinase-interacting protein 1B [auth F]11Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UQF2 (Homo sapiens)
Explore Q9UQF2 
Go to UniProtKB:  Q9UQF2
PHAROS:  Q9UQF2
GTEx:  ENSG00000121653 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UQF2
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.81 Å
  • R-Value Free: 0.315 
  • R-Value Work: 0.249 
  • R-Value Observed: 0.252 
  • Space Group: P 63 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 161.781α = 90
b = 161.781β = 90
c = 87.725γ = 120
Software Package:
Software NamePurpose
ADSCdata collection
PHASESphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-02-13
    Type: Initial release
  • Version 1.1: 2019-12-04
    Changes: Data collection, Database references
  • Version 1.2: 2024-03-20
    Changes: Data collection, Database references