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PDBsum entry 3vum

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protein ligands Protein-protein interface(s) links
Transferase/transferase inhibitor PDB id
3vum
Jmol
Contents
Protein chains
347 a.a.
11 a.a.
Ligands
SO4
TRS
Waters ×84
PDB id:
3vum
Name: Transferase/transferase inhibitor
Title: Crystal structure of a cysteine-deficient mutant m7 in map k
Structure: Mitogen-activated protein kinase 8. Chain: a. Fragment: kinase domain, unp residues 1-364. Synonym: mitogen-activated protein kinase 8 isoform jnk1 be mitogen-activated protein kinase 8, isoform cra_d, cdna flj highly similar to homo sapiens mitogen-activated protein ki (mapk8), transcript variant 4, mRNA. Engineered: yes. Mutation: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606
Resolution:
2.69Å     R-factor:   0.192     R-free:   0.255
Authors: T.Nakaniwa,T.Kinoshita,T.Inoue
Key ref: T.Nakaniwa et al. (2012). 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. Biochemistry, 51, 8410-8421. PubMed id: 23020677 DOI: 10.1021/bi300918w
Date:
02-Jul-12     Release date:   13-Feb-13    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P45983  (MK08_HUMAN) -  Mitogen-activated protein kinase 8
Seq:
Struc:
427 a.a.
347 a.a.*
Protein chain
Pfam   ArchSchema ?
Q9UQF2  (JIP1_HUMAN) -  C-Jun-amino-terminal kinase-interacting protein 1
Seq:
Struc:
 
Seq:
Struc:
711 a.a.
11 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 18 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain A: E.C.2.7.11.24  - Mitogen-activated protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
= ADP
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     protein phosphorylation   1 term 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi300918w Biochemistry 51:8410-8421 (2012)
PubMed id: 23020677  
 
 
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.
T.Nakaniwa, H.Fukada, T.Inoue, M.Gouda, R.Nakai, Y.Kirii, M.Adachi, T.Tamada, S.Segawa, R.Kuroki, T.Tada, T.Kinoshita.
 
  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.