title: The crystal structure of JNK from Drosophila melanogaster reveals an evolutionarily conserved topology with that of mammalian JNK proteins.
abstract: BACKGROUND
  The c-Jun N-terminal kinases (JNKs), members of the mitogen-activated protein kinase (MAPK) family, engage in diverse cellular responses to signals produced under normal development and stress conditions. In Drosophila, only one JNK member is present, whereas ten isoforms from three JNK genes (JNK1, 2, and 3) are present in mammalian cells. To date, several mammalian JNK structures have been determined, however, there has been no report of any insect JNK structure.
  
  
  RESULTS
  We report the first structure of JNK from Drosophila melanogaster (DJNK). The crystal structure of the unphosphorylated form of DJNK complexed with adenylyl imidodiphosphate (AMP-PNP) has been solved at 1.79 Å resolution. The fold and topology of DJNK are similar to those of mammalian JNK isoforms, demonstrating their evolutionarily conserved structures and functions. Structural comparisons of DJNK and the closely related mammalian JNKs also allow identification of putative catalytic residues, substrate-binding sites and conformational alterations upon docking interaction with Drosophila scaffold proteins.
  
  
  CONCLUSIONS
  The DJNK structure reveals common features with those of the mammalian JNK isoforms, thereby allowing the mapping of putative catalytic and substrate binding sites. Additionally, structural changes upon peptide binding could be predicted based on the comparison with the closely-related JNK3 structure in complex with pepJIP1. This is the first structure of insect JNK reported to date, and will provide a platform for future mutational studies in Drosophila to ascertain the functional role of insect JNK.
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom, 73170, Thailand. sarin.chi@mahidol.ac.th.
authors.forename: Sarin
authors.initials: S
authors.lastname: Chimnaronk
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom, 73170, Thailand. robben16_chelsea@hotmail.com.
authors.forename: Jatuporn
authors.initials: J
authors.lastname: Sitthiroongruang
authors.affiliation: Faculty of Allied Health Sciences, Burapha University, Mueang District, Saen Sook, Chonburi, 20131, Thailand. kanokporns@buu.ac.th.
authors.forename: Kanokporn
authors.initials: K
authors.lastname: Srisucharitpanit
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom, 73170, Thailand. catta_w255@hotmail.co.th.
authors.forename: Monrudee
authors.initials: M
authors.lastname: Srisaisup
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom, 73170, Thailand. albert.ket@mahidol.ac.th.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Ketterman
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom, 73170, Thailand. panadda.boo@mahidol.ac.th.
authors.forename: Panadda
authors.initials: P
authors.lastname: Boonserm
mesh_terms: D000266:Adenylyl Imidodiphosphate / Q000378:metabolism*; D000818:Animals; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000737:chemistry / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D017433:Protein Structure, Secondary
chemical_list: D029721:Drosophila Proteins; D000266:Adenylyl Imidodiphosphate; C117694:Hep protein, Drosophila; D020929:Mitogen-Activated Protein Kinase Kinases; D008274:Magnesium