title: Structure of anabolic ornithine carbamoyltransferase from Campylobacter jejuni at 2.7 Å resolution.
abstract: Anabolic ornithine transcarbamoylase (aOTC) catalyzes the reaction between carbamoyl phosphate (CP) and L-ornithine (ORN) to form L-citrulline and phosphate in the urea cycle and L-arginine biosynthesis. The crystal structure of unliganded aOTC from Campylobacter jejuni (Cje aOTC) was determined at 2.7 Å resolution and refined to an R(work) of 20.3% and an R(free) of 24.0%. Cje aOTC is a trimer that forms a head-to-head pseudohexamer in the asymmetric unit. Each monomer is composed of an N-terminal CP-binding domain and a C-terminal ORN-binding domain joined by two interdomain helices. The Cje aOTC structure presents an open conformation of the enzyme with a relatively flexible orientation of the ORN-binding domain respective to the CP-binding domain. The conformation of the B2-H3 loop (residues 68-78), which is involved in binding CP in an adjacent subunit of the trimer, differs from that seen in homologous proteins with CP bound. The loop containing the ORN-binding motif (DxxxSMG, residues 223-230) has a conformation that is different from those observed in unliganded OTC structures from other species, but is similar to those in structures with bound ORN analogs. The major differences in tertiary structure between Cje aOTC and human aOTC are described.
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA 22908, USA.
authors.forename: I G
authors.initials: IG
authors.lastname: Shabalin
authors.forename: P J
authors.initials: PJ
authors.lastname: Porebski
authors.forename: D R
authors.initials: DR
authors.lastname: Cooper
authors.forename: M
authors.initials: M
authors.lastname: Grabowski
authors.forename: O
authors.initials: O
authors.lastname: Onopriyenko
authors.forename: S
authors.initials: S
authors.lastname: Grimshaw
authors.forename: A
authors.initials: A
authors.lastname: Savchenko
authors.forename: M
authors.initials: M
authors.lastname: Chruszcz
authors.forename: W
authors.initials: W
authors.lastname: Minor
mesh_terms: D000595:Amino Acid Sequence; D016123:Campylobacter jejuni / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009954:Ornithine Carbamoyltransferase / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
chemical_list: D009954:Ornithine Carbamoyltransferase