title: Crystal structure of transglutaminase 2 with GTP complex and amino acid sequence evidence of evolution of GTP binding site.
abstract: Transglutaminase2 (TG2) is a multi-functional protein involved in various cellular processes, including apoptosis, differentiation, wound healing, and angiogenesis. The malfunction of TG2 causes many human disease including inflammatory disease, celiac disease, neurodegenerative diseases, tissue fibrosis, and cancers. Protein cross-linking activity, which is representative of TG2, is activated by calcium ions and suppressed by GTP. Here, we elucidated the structure of TG2 in complex with its endogenous inhibitor, GTP. Our structure showed why GTP is the optimal nucleotide for interacting with and inhibiting TG2. In addition, sequence comparison provided information describing the evolutionary scenario of GTP usage for controlling the activity of TG2.
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan, South Korea; Graduate School of Biochemistry, Yeungnam University, Gyeongsan, South Korea.
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Jang
authors.affiliation: Department of Physiology and Biophysics at Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Dong-Sup
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Korea University, Seoul, South Korea.
authors.forename: Kihang
authors.initials: K
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Molecular Biology/Aging and Apoptosis Research Center (AARC), Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Eui Man
authors.initials: EM
authors.lastname: Jeong
authors.affiliation: Department of Biochemistry and Molecular Biology/Aging and Apoptosis Research Center (AARC), Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: In-Gyu
authors.initials: IG
authors.lastname: Kim
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Department of Physiology, Department of Biomedical Sciences, and Institute of Dermatological Science, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Jung Nyeo
authors.initials: JN
authors.lastname: Chun
authors.affiliation: Department of Physiology, Department of Biomedical Sciences, and Institute of Dermatological Science, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan, South Korea; Graduate School of Biochemistry, Yeungnam University, Gyeongsan, South Korea.
authors.forename: Hyun Ho
authors.initials: HH
authors.lastname: Park
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D011503:Transglutaminases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D006160:Guanosine Triphosphate; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins