Structure of human argininosuccinate synthetase.
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).
Karlberg
Tobias
T
Structural Genomics Consortium, Karolinska Institutet, MBB/SGC, 171 77 Stockholm, Sweden.
Collins
Ruairi
R
van den Berg
Susanne
S
Flores
Alex
A
Hammarström
Martin
M
Högbom
Martin
M
Holmberg Schiavone
Lovisa
L
Uppenberg
Jonas
J
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
D000255:Adenosine Triphosphate; D001124:Argininosuccinate Synthase