1S3I

Crystal structure of the N terminal hydrolase domain of 10-formyltetrahydrofolate dehydrogenase

1S3I の概要

• エントリーDOI: 10.2210/pdb1s3i/pdb
• 分子名称: 10-formyltetrahydrofolate dehydrogenase, BETA-MERCAPTOETHANOL (3 entities in total)
• 機能のキーワード: rossmann fold, hydrolase, oxidoreductase
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Cytoplasm: P28037
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34472.50

構造登録者

Chumanevich, A.A.,Krupenko, S.A.,Davies, C. (登録日: 2004-01-13, 公開日: 2004-01-27, 最終更新日: 2021-10-27)

主引用文献

Chumanevich, A.A.,Krupenko, S.A.,Davies, C.
The crystal structure of the hydrolase domain of 10-formyltetrahydrofolate dehydrogenase: mechanism of hydrolysis and its interplay with the dehydrogenase domain.
J.Biol.Chem., 279:14355-14364, 2004

PubMed Abstract: 10-Formyltetrahydrofolate dehydrogenase (FDH) converts 10-formyltetrahydrofolate, a precursor for nucleotide biosynthesis, to tetrahydrofolate. The protein comprises two functional domains: a hydrolase domain that removes a formyl group from 10-formyltetrahydrofolate and a NADP(+)-dependent dehydrogenase domain that reduces the formyl to carbon dioxide. As a first step toward deciphering the catalytic mechanism of the enzyme, we have determined the crystal structure of the hydrolase domain of FDH from rat, solved to 2.3-A resolution. The structure comprises two domains. As expected, domain 1 shares the same Rossmann fold as the related enzymes, methionyl-tRNA-formyltransferase and glycinamide ribonucleotide formyltransferase, but, unexpectedly, the structural similarity between the amino-terminal domain of 10-formyltetrahydrofolate dehydrogenase and methionyl-tRNA-formyltransferase extends to the C terminus of both proteins. The active site contains a molecule of beta-mercaptoethanol that is positioned between His-106 and Asp-142 and that appears to mimic the formate product. We propose a catalytic mechanism for the hydrolase reaction in which Asp-142 polarizes the catalytic water molecule and His-106 orients the carbonyl group of formyl. The structure also provides clues as to how, in the native enzyme, the hydrolase domain transfers its product to the dehydrogenase domain.

PubMed: 14729668
DOI: 10.1074/jbc.M313934200

実験手法

X-RAY DIFFRACTION (2.3 Å)