7C7C
Crystal structure of human TRAP1 with SJT104
Summary for 7C7C
| Entry DOI | 10.2210/pdb7c7c/pdb |
| Descriptor | Heat shock protein 75 kDa, mitochondrial, 2-azanyl-9-[(4-bromanyl-2-fluoranyl-phenyl)methyl]-6-chloranyl-purin-8-ol (2 entities in total) |
| Functional Keywords | trpa1, selectivity, mitochondria, hsp90, anticancer, drug, chaperone |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 57794.67 |
| Authors | Kim, D.,Yang, S.,Yoon, N.G.,Park, E.,Kim, S.Y.,Kang, B.H.,Lee, C.,Kang, S. (deposition date: 2020-05-24, release date: 2021-05-26, Last modification date: 2023-11-29) |
| Primary citation | Yang, S.,Yoon, N.G.,Kim, D.,Park, E.,Kim, S.Y.,Lee, J.H.,Lee, C.,Kang, B.H.,Kang, S. Design and Synthesis of TRAP1 Selective Inhibitors: H-Bonding with Asn171 Residue in TRAP1 Increases Paralog Selectivity. Acs Med.Chem.Lett., 12:1173-1180, 2021 Cited by PubMed Abstract: Tumor necrosis factor receptor-associated protein 1 (TRAP1) is overexpressed in the mitochondria of various cancer cells, reprograms cellular metabolism to enable cancer cells to adapt to harsh tumor environments. As inactivation of TRAP1 induces massive apoptosis in cancer cells and , the development of TRAP1-selective inhibitors has become an attractive approach. A series of purine-8-one and pyrrolo[2,3-]pyrimidine derivatives was developed based on TRAP1 structure and identified to be highly selective in vitro for TRAP1 over the paralogous enzymes, Hsp90α and Grp94. The TRAP1-selective inhibition strategy via utilization of the Asn171 residue of the ATP-lid was investigated using X-ray crystallography and molecular dynamics simulation studies. Among various synthesized potent TRAP1 inhibitors, possessed a 65-fold selectivity over Hsp90α and a 13-fold selectivity over Grp94. Additionally, had a half-maximal inhibitory concentration (IC) of 63.5 nM for TRAP1, with a 78-fold and 30-fold selectivity over Hsp90α and Grp94, respectively. PubMed: 34267888DOI: 10.1021/acsmedchemlett.1c00213 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3 Å) |
Structure validation
Download full validation report
