EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural basis for substrate binding, catalysis, and inhibition of cancer target mitochondrial creatine kinase by a covalent inhibitor.
ジャーナル・号・ページ	Structure, Vol. 33, Issue 4, Page 786-797.e3, Year 2025
掲載日	2025年4月3日
著者	Merve Demir / Laura Koepping / Ya Li / Lynn Fujimoto / Andrey Bobkov / Jianhua Zhao / Taro Hitosugi / Eduard Sergienko /
PubMed 要旨	Mitochondrial creatine kinases (MtCKs) are key players in maintaining energy homeostasis in cells that work with cytosolic creatine kinases for energy transport from mitochondria to cytoplasm. The ...Mitochondrial creatine kinases (MtCKs) are key players in maintaining energy homeostasis in cells that work with cytosolic creatine kinases for energy transport from mitochondria to cytoplasm. The inhibition of breast cancer growth by cyclocreatine targeting CKs indicates dependence of cancer cells on the "energy shuttle" for cell growth and survival. Hence, understanding key mechanistic features of creatine kinases and their inhibition plays an important role in the development of cancer therapeutics. Herein, we present mutational and structural investigations on understudied ubiquitous MtCK that showed closure of the loop comprising His61 is specific to and relies on creatine binding and mechanism of phosphoryl transfer depends on electrostatics of active site. We demonstrate that previously identified pan-CK covalent inhibitor CKi inhibit breast cancer cell proliferation; however, our biochemical and structural data indicated that inhibition by CKi is highly dependent on covalent link formation and conformational changes upon creatine binding are not observed.
リンク	Structure / PubMed:39904336 / PubMed Central
手法	EM (単粒子)
解像度	2.2 - 2.89 Å
構造データ	44028 9b04 EMDB-44028, PDB-9b04: Cryo-EM structure of human uMtCK1 in complex with ADP 手法: EM (単粒子) / 解像度: 2.52 Å 44029 9b05 EMDB-44029, PDB-9b05: Cryo-EM structure of human uMtCK1 手法: EM (単粒子) / 解像度: 2.4 Å 44055 9b0t EMDB-44055, PDB-9b0t: Cryo-EM structure of E227Q variant of uMtCK1 in complex with transition state analog 手法: EM (単粒子) / 解像度: 2.3 Å 44058 9b0u EMDB-44058, PDB-9b0u: Cryo-EM structure of E227Q variant of uMtCK1 incubated with ADP and phosphocreatine at pH 8.0 手法: EM (単粒子) / 解像度: 2.44 Å 44068 9b14 EMDB-44068, PDB-9b14: Cryo-EM structure of human uMtCK1 in complex with transition state analog 手法: EM (単粒子) / 解像度: 2.2 Å 44069 9b16 EMDB-44069, PDB-9b16: Cryo-EM structure of human uMtCK1 in complex with ADP and covalent inhibitor CKi 手法: EM (単粒子) / 解像度: 2.89 Å
化合物	ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-CRN: N-[(E)-AMINO(IMINO)METHYL]-N-METHYLGLYCINE / クレアチン ChemComp-NO3: NITRATE ION ChemComp-PO4: PHOSPHATE ION / ホスファ-ト ChemComp-KLU*: (2S)-4-(chloroacetyl)-3,4-dihydro-2H-1,4-benzoxazine-2-carboxamide
由来	homo sapiens (ヒト)
キーワード	TRANSFERASE / mitochondrial creatine kinase / TRANSFERASE/INHIBITOR / TRANSFERASE-INHIBITOR complex