1FVO

CRYSTAL STRUCTURE OF HUMAN ORNITHINE TRANSCARBAMYLASE COMPLEXED WITH CARBAMOYL PHOSPHATE

1FVO の概要

• エントリーDOI: 10.2210/pdb1fvo/pdb
• 関連するPDBエントリー: 1C9Y 1EP9 1OTH
• 分子名称: ORNITHINE TRANSCARBAMYLASE, PHOSPHORIC ACID MONO(FORMAMIDE)ESTER (3 entities in total)
• 機能のキーワード: two domains, alpha/beta topology, 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: 2
• 化学式量合計: 72495.14

構造登録者

Shi, D.,Morizono, H.,Yu, X.,Allewell, N.M.,Tuchman, M. (登録日: 2000-09-20, 公開日: 2001-04-04, 最終更新日: 2024-05-22)

主引用文献

Shi, D.,Morizono, H.,Yu, X.,Tong, L.,Allewell, N.M.,Tuchman, M.
Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes.
Biochem.J., 354:501-509, 2001

PubMed Abstract: Two crystal structures of human ornithine transcarbamylase (OTCase) complexed with the substrate carbamoyl phosphate (CP) have been solved. One structure, whose crystals were prepared by substituting N-phosphonacetyl-L-ornithine (PALO) liganded crystals with CP, has been refined at 2.4 A (1 A=0.1 nm) resolution to a crystallographic R factor of 18.4%. The second structure, whose crystals were prepared by co-crystallization with CP, has been refined at 2.6 A resolution to a crystallographic R factor of 20.2%. These structures provide important new insights into substrate recognition and ligand-induced conformational changes. Comparison of these structures with the structures of OTCase complexed with the bisubstrate analogue PALO or CP and L-norvaline reveals that binding of the first substrate, CP, induces a global conformational change involving relative domain movement, whereas the binding of the second substrate brings the flexible SMG loop, which is equivalent to the 240s loop in aspartate transcarbamylase, into the active site. The model reveals structural features that define the substrate specificity of the enzyme and that regulate the order of binding and release of products.

PubMed: 11237854
DOI: 10.1042/0264-6021:3540501

実験手法

X-RAY DIFFRACTION (2.6 Å)