1OTH

CRYSTAL STRUCTURE OF HUMAN ORNITHINE TRANSCARBAMOYLASE COMPLEXED WITH N-PHOSPHONACETYL-L-ORNITHINE

1OTH の概要

• エントリーDOI: 10.2210/pdb1oth/pdb
• 分子名称: PROTEIN (ORNITHINE TRANSCARBAMOYLASE), N-(PHOSPHONOACETYL)-L-ORNITHINE (3 entities in total)
• 機能のキーワード: transcarbamoylase, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion matrix: P00480
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36360.73

構造登録者

Shi, D.,Morizono, H.,Ha, Y.,Aoyagi, M.,Tuchman, N.,Allewell, N.M. (登録日: 1998-10-06, 公開日: 1999-10-06, 最終更新日: 2023-08-16)

主引用文献

Shi, D.,Morizono, H.,Ha, Y.,Aoyagi, M.,Tuchman, M.,Allewell, N.M.
1.85-A resolution crystal structure of human ornithine transcarbamoylase complexed with N-phosphonacetyl-L-ornithine. Catalytic mechanism and correlation with inherited deficiency.
J.Biol.Chem., 273:34247-34254, 1998

PubMed Abstract: The crystal structure of human ornithine transcarbamoylase complexed with the bisubstrate analog N-phosphonacetyl-L-ornithine has been solved at 1.85-A resolution by molecular replacement. Deleterious mutations produce clinical hyperammonia that, if untreated, results in neurological symptoms or death (ornithine transcarbamylase deficiency). The holoenzyme is trimeric, and as in other transcarbamoylases, each subunit contains an N-terminal domain that binds carbamoyl phosphate and a C-terminal domain that binds L-ornithine. The active site is located in the cleft between domains and contains additional residues from an adjacent subunit. Binding of N-phosphonacetyl-L-ornithine promotes domain closure. The resolution of the structure enables the role of active site residues in the catalytic mechanism to be critically examined. The side chain of Cys-303 is positioned so as to be able to interact with the delta-amino group of L-ornithine which attacks the carbonyl carbon of carbamoyl phosphate in the enzyme-catalyzed reaction. This sulfhydryl group forms a charge relay system with Asp-263 and the alpha-amino group of L-ornithine, instead of with His-302 and Glu-310, as previously proposed. In common with other ureotelic ornithine transcarbamoylases, the human enzyme lacks a loop of approximately 20 residues between helix H10 and beta-strand B10 which is present in prokaryotic ornithine transcarbamoylases but has a C-terminal extension of 10 residues that interacts with the body of the protein but is exposed. The sequence of this C-terminal extension is homologous to an interhelical loop found in several membrane proteins, including mitochondrial transport proteins, suggesting a possible mode of interaction with the inner mitochondrial membrane.

PubMed: 9852088
DOI: 10.1074/jbc.273.51.34247

実験手法

X-RAY DIFFRACTION (1.85 Å)