Loading
PDBj
メニューPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDBDonate
RCSB PDBPDBeBMRBAdv. SearchSearch help

5K9C

Crystal structure of human dihydroorotate dehydrogenase with ML390

5K9C の概要
エントリーDOI10.2210/pdb5k9c/pdb
関連するPDBエントリー5K9D
分子名称Dihydroorotate dehydrogenase (quinone), mitochondrial, 1-DEOXY-1-(7,8-DIMETHYL-2,4-DIOXO-3,4-DIHYDRO-2H-BENZO[G]PTERIDIN-1-ID-10(5H)-YL)-5-O-PHOSPHONATO-D-RIBITOL, OROTIC ACID, ... (9 entities in total)
機能のキーワードoxidoreductase, alpha/beta barrel, inhibitor, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
由来する生物種Homo sapiens (Human)
細胞内の位置Mitochondrion inner membrane ; Single-pass membrane protein : Q02127
タンパク質・核酸の鎖数1
化学式量合計41496.72
構造登録者
Lewis, T.A.,Sykes, D.B.,Law, J.M.,Munoz, B.,Scadden, D.T.,Rustiguel, J.K.,Nonato, M.C.,Schreiber, S.L. (登録日: 2016-05-31, 公開日: 2016-10-12, 最終更新日: 2023-09-27)
主引用文献Lewis, T.A.,Sykes, D.B.,Law, J.M.,Munoz, B.,Rustiguel, J.K.,Nonato, M.C.,Scadden, D.T.,Schreiber, S.L.
Development of ML390: A Human DHODH Inhibitor That Induces Differentiation in Acute Myeloid Leukemia.
ACS Med Chem Lett, 7:1112-1117, 2016
Cited by
PubMed Abstract: Homeobox transcription factor A9 (HoxA9) is overexpressed in 70% of patients diagnosed with acute myeloid leukemia (AML), whereas only a small subset of AML patients respond to current differentiation therapies. A cell line overexpressing HoxA9 was derived from the bone marrow of a lysozyme-GFP mouse. In this fashion, GFP served as an endogenous reporter of differentiation, permitting a high-throughput phenotypic screen against the MLPCN library. Two chemical scaffolds were optimized for activity yielding compound ML390, and genetic resistance and sequencing efforts identified dihydroorotate dehydrogenase (DHODH) as the target enzyme. The DHODH inhibitor brequinar works against these leukemic cells as well. The X-ray crystal structure of ML390 bound to DHODH elucidates ML390s binding interactions.
PubMed: 27994748
DOI: 10.1021/acsmedchemlett.6b00316
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (1.66 Å)
構造検証レポート
Validation report summary of 5k9c
検証レポート(詳細版)ダウンロードをダウンロード

243531

件を2025-10-22に公開中

PDB statisticsPDBj update infoContact PDBjnumon