2X2R
Crystal structure of human kinesin Eg5 in complex with (R)-2-amino-3-((4-chlorophenyl)diphenylmethylthio)propanoic acid
Summary for 2X2R
| Entry DOI | 10.2210/pdb2x2r/pdb |
| Related | 1II6 1Q0B 1X88 1YRS 2FKY 2FL2 2FL6 2G1Q 2GM1 2UYI 2UYM 2WOG |
| Descriptor | KINESIN-LIKE PROTEIN KIF11, ADENOSINE-5'-DIPHOSPHATE, (2R)-2-AMINO-3-[(2R)-2-METHYL-1,1-DIPHENYL-BUTYL]SULFANYL-PROPANOIC ACID, ... (5 entities in total) |
| Functional Keywords | mitosis, cell cycle, microtubule, atp-binding, motor protein, cell division |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Cytoplasm: P52732 |
| Total number of polymer chains | 3 |
| Total formula weight | 125551.71 |
| Authors | Kaan, H.Y.K.,Weiss, J.,Menger, D.,Ulaganathan, V.,Laggner, C.,Popowycz, F.,Joseph, B.,Kozielski, F. (deposition date: 2010-01-15, release date: 2011-01-26, Last modification date: 2023-12-20) |
| Primary citation | Kaan, H.Y.K.,Weiss, J.,Menger, D.,Ulaganathan, V.,Tkocz, K.,Laggner, C.,Popowycz, F.,Joseph, B.,Kozielski, F. Structure-Activity Relationship and Multidrug Resistance Study of New S-Trityl-L-Cysteine Derivatives as Inhibitors of Eg5. J.Med.Chem., 54:1576-, 2011 Cited by PubMed Abstract: The mitotic spindle is a validated target for cancer chemotherapy. Drugs such as taxanes and vinca alkaloids specifically target microtubules and cause the mitotic spindle to collapse. However, toxicity and resistance are problems associated with these drugs. Thus, alternative approaches to inhibiting the mitotic spindle are being pursued. These include targeting Eg5, a human kinesin involved in the formation of the bipolar spindle. We previously identified S-trityl-L-cysteine (STLC) as a potent allosteric inhibitor of Eg5. Here, we report the synthesis of a new series of STLC-like compounds with in vitro inhibition in the low nanomolar range. We also performed a multidrug resistance study in cell lines overexpressing P-glycoprotein and showed that some of these inhibitors may have the potential to overcome susceptibility to this efflux pump. Finally, we performed molecular docking of the compounds and determined the structures of two Eg5-inhibitor complexes to explain the structure-activity relationship of these compounds. PubMed: 21344920DOI: 10.1021/JM100991M PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
Download full validation report
