Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural basis for substrate binding, catalysis, and inhibition of cancer target mitochondrial creatine kinase by a covalent inhibitor.
Journal, issue, pages	Structure, Vol. 33, Issue 4, Page 786-797.e3, Year 2025
Publish date	Apr 3, 2025
Authors	Merve Demir / Laura Koepping / Ya Li / Lynn Fujimoto / Andrey Bobkov / Jianhua Zhao / Taro Hitosugi / Eduard Sergienko /
PubMed Abstract	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.
External links	Structure / PubMed:39904336 / PubMed Central
Methods	EM (single particle)
Resolution	2.2 - 2.89 Å
Structure data	44028 9b04 EMDB-44028, PDB-9b04: Cryo-EM structure of human uMtCK1 in complex with ADP Method: EM (single particle) / Resolution: 2.52 Å 44029 9b05 EMDB-44029, PDB-9b05: Cryo-EM structure of human uMtCK1 Method: EM (single particle) / Resolution: 2.4 Å 44055 9b0t EMDB-44055, PDB-9b0t: Cryo-EM structure of E227Q variant of uMtCK1 in complex with transition state analog Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 2.44 Å 44068 9b14 EMDB-44068, PDB-9b14: Cryo-EM structure of human uMtCK1 in complex with transition state analog Method: EM (single particle) / Resolution: 2.2 Å 44069 9b16 EMDB-44069, PDB-9b16: Cryo-EM structure of human uMtCK1 in complex with ADP and covalent inhibitor CKi Method: EM (single particle) / Resolution: 2.89 Å
Chemicals	ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM ChemComp-MG: Unknown entry ChemComp-CRN: N-[(E)-AMINO(IMINO)METHYL]-N-METHYLGLYCINE ChemComp-NO3: NITRATE ION ChemComp-PO4: PHOSPHATE ION ChemComp-KLU*: (2S)-4-(chloroacetyl)-3,4-dihydro-2H-1,4-benzoxazine-2-carboxamide
Source	homo sapiens (human)
Keywords	TRANSFERASE / mitochondrial creatine kinase / TRANSFERASE/INHIBITOR / TRANSFERASE-INHIBITOR complex