2DOR

DIHYDROOROTATE DEHYDROGENASE A FROM LACTOCOCCUS LACTIS COMPLEXED WITH OROTATE

2DOR の概要

• エントリーDOI: 10.2210/pdb2dor/pdb
• 分子名称: DIHYDROOROTATE DEHYDROGENASE A, FLAVIN MONONUCLEOTIDE, OROTIC ACID, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, pyrimidine nucleotide biosynthesis
• 由来する生物種: Lactococcus lactis
• 細胞内の位置: Cytoplasm (By similarity): P54321
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69709.22

構造登録者

Rowland, P.,Larsen, S. (登録日: 1998-05-11, 公開日: 1998-08-12, 最終更新日: 2024-02-14)

主引用文献

Rowland, P.,Bjornberg, O.,Nielsen, F.S.,Jensen, K.F.,Larsen, S.
The crystal structure of Lactococcus lactis dihydroorotate dehydrogenase A complexed with the enzyme reaction product throws light on its enzymatic function.
Protein Sci., 7:1269-1279, 1998

PubMed Abstract: Dihydroorotate dehydrogenases (DHODs) catalyze the oxidation of (S)-dihydroorotate to orotate, the fourth step and only redox reaction in the de novo biosynthesis of pyrimidine nucleotides. A description is given of the crystal structure of Lactococcus lactis dihydroorotate dehydrogenase A (DHODA) complexed with the product of the enzyme reaction orotate. The structure of the complex to 2.0 A resolution has been compared with the structure of the native enzyme. The active site of DHODA is known to contain a water filled cavity buried beneath a highly conserved and flexible loop. In the complex the orotate displaces the water molecules from the active site and stacks above the DHODA flavin isoalloxazine ring, causing only small movements of the surrounding protein residues. The orotate is completely buried beneath the protein surface, and the orotate binding causes a significant reduction in the mobility of the active site loop. The orotate is bound by four conserved asparagine side chains (Asn 67, Asn 127, Asn 132, and Asn 193), the side chains of Lys 43 and Ser 194, and the main chain NH groups of Met 69, Gly 70, and Leu 71. Of these the Lys 43 side chain makes hydrogen bonds to both the flavin isoalloxazine ring and the carboxylate group of the orotate. Potential interactions with bound dihydroorotate are considered using the orotate complex as a basis for molecular modeling. The role of Cys 130 as the active site base is discussed, and the sequence conservation of the active site residues across the different families of DHODs is reviewed, along with implications for differences in substrate binding and in the catalytic mechanisms between these families.

PubMed: 9655329

実験手法

X-RAY DIFFRACTION (2 Å)