title: The emerging structural understanding of transglutaminase 3.
abstract: Transglutaminases (TGase; protein-glutamine: amine gamma-glutamyl-transferase) are a family of calcium-dependent acyl-transfer enzymes ubiquitously expressed in mammalian cells and responsible for catalyzing covalent cross-links between proteins or peptides. A series of recent crystal structures have revealed the overall architecture of TGase enzymes, and provided a deep look at their active site, calcium and magnesium ions, and the manner by which guanine nucleotides interact with this enzyme. These structures, backed with extensive biochemical studies, are providing new insights as to how access to the enzyme's active site may be gated through the coordinated changes in cellular calcium and magnesium concentrations and GTP/GDP. Calcium-activated TGase 3 can bind, hydrolyze, and is inhibited by GTP, despite lacking structural homology with other GTP binding proteins. A structure based sequence homology among the TGase enzyme family shows that these essential structural features are shared among other members of the TGase family.
authors.affiliation: X-ray Crystallography Facility, Office of Science and Technology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-8023, USA. Ahvazib@mail.nih.gov
authors.forename: Bijan
authors.initials: B
authors.lastname: Ahvazi
authors.forename: Karen M
authors.initials: KM
authors.lastname: Boeshans
authors.forename: Fraydoon
authors.initials: F
authors.lastname: Rastinejad
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008670:Metals / Q000378:metabolism; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011503:Transglutaminases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D008670:Metals; D006160:Guanosine Triphosphate; C498712:TGM3 protein, human; D011503:Transglutaminases