title: Structure of human argininosuccinate synthetase.
abstract: Argininosuccinate synthetase catalyzes the transformation of citrulline and aspartate into argininosuccinate and pyrophosphate using the hydrolysis of ATP to AMP and pyrophosphate. This enzymatic process constitutes the rate-limiting step in both the urea and arginine-citrulline cycles. Previous studies have investigated the crystal structures of argininosuccinate synthetase from bacterial species. In this work, the first crystal structure of human argininosuccinate synthetase in complex with the substrates citrulline and aspartate is presented. The human enzyme is compared with structures of argininosuccinate synthetase from bacteria. In addition, the structure also provides new insights into the function of the numerous clinical mutations identified in patients with type I citrullinaemia (also known as classic citrullinaemia).
authors.affiliation: Structural Genomics Consortium, Karolinska Institutet, MBB/SGC, 171 77 Stockholm, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Karlberg
authors.forename: Ruairi
authors.initials: R
authors.lastname: Collins
authors.forename: Susanne
authors.initials: S
authors.lastname: van den Berg
authors.forename: Alex
authors.initials: A
authors.lastname: Flores
authors.forename: Martin
authors.initials: M
authors.lastname: Hammarström
authors.forename: Martin
authors.initials: M
authors.lastname: Högbom
authors.forename: Lovisa
authors.initials: L
authors.lastname: Holmberg Schiavone
authors.forename: Jonas
authors.initials: J
authors.lastname: Uppenberg
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D001124:Argininosuccinate Synthase / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020539:Sequence Analysis, Protein; D013379:Substrate Specificity
chemical_list: D000255:Adenosine Triphosphate; D001124:Argininosuccinate Synthase