2OTC

ORNITHINE TRANSCARBAMOYLASE COMPLEXED WITH N-(PHOSPHONACETYL)-L-ORNITHINE

Summary for 2OTC

• Entry DOI: 10.2210/pdb2otc/pdb
• Descriptor: ORNITHINE CARBAMOYLTRANSFERASE, N-(PHOSPHONOACETYL)-L-ORNITHINE (3 entities in total)
• Functional Keywords: transferase, otcase, ornithine, transcarbamoylase, arginine synthesis, urea cycle
• Biological source: Escherichia coli BL21(DE3)
• Cellular location: Cytoplasm (Probable): P04391
• Total number of polymer chains: 9
• Total formula weight: 334288.18

Authors

Ha, Y.,Allewell, N.M. (deposition date: 1997-06-15, release date: 1998-06-17, Last modification date: 2024-05-22)

Primary citation

Ha, Y.,McCann, M.T.,Tuchman, M.,Allewell, N.M.
Substrate-induced conformational change in a trimeric ornithine transcarbamoylase.
Proc.Natl.Acad.Sci.USA, 94:9550-9555, 1997

PubMed Abstract: The crystal structure of Escherichia coli ornithine transcarbamoylase (OTCase, EC 2.1.3.3) complexed with the bisubstrate analog N-(phosphonacetyl)-L-ornithine (PALO) has been determined at 2.8-A resolution. This research on the structure of a transcarbamoylase catalytic trimer with a substrate analog bound provides new insights into the linkages between substrate binding, protein-protein interactions, and conformational change. The structure was solved by molecular replacement with the Pseudomonas aeruginosa catabolic OTCase catalytic trimer (Villeret, V., Tricot, C., Stalon, V. & Dideberg, O. (1995) Proc. Natl. Acad. Sci. USA 92, 10762-10766; Protein Data Bank reference pdb 1otc) as the model and refined to a crystallographic R value of 21.3%. Each polypeptide chain folds into two domains, a carbamoyl phosphate binding domain and an L-ornithine binding domain. The bound inhibitor interacts with the side chains and/or backbone atoms of Lys-53, Ser-55, Thr-56, Arg-57, Thr-58, Arg-106, His-133, Asn-167, Asp-231, Met-236, Leu-274, Arg-319 as well as Gln-82 and Lys-86 from an adjacent chain. Comparison with the unligated P. aeruginosa catabolic OTCase structure indicates that binding of the substrate analog results in closure of the two domains of each chain. As in E. coli aspartate transcarbamoylase, the 240s loop undergoes the largest conformational change upon substrate binding. The clinical implications for human OTCase deficiency are discussed.

PubMed: 9275160
DOI: 10.1073/pnas.94.18.9550

Experimental method

X-RAY DIFFRACTION (2.8 Å)