4A5Y
Intermediate state of human kinesin Eg5 in complex with Ispinesib
Summary for 4A5Y
| Entry DOI | 10.2210/pdb4a5y/pdb |
| Related | 1II6 1Q0B 1X88 1YRS 2FKY 2FL2 2FL6 2G1Q 2GM1 2UYI 2UYM 2WOG 2X2R 2X7C 2X7D 2X7E 2XAE 4A1Z 4A28 4A50 4A51 |
| Descriptor | KINESIN-LIKE PROTEIN KIF11, ADENOSINE-5'-DIPHOSPHATE, CHLORIDE ION, ... (7 entities in total) |
| Functional Keywords | motor protein, mitosis |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Cytoplasm : P52732 |
| Total number of polymer chains | 3 |
| Total formula weight | 126284.69 |
| Authors | Kaan, H.Y.K.,Kozielski, F. (deposition date: 2011-10-29, release date: 2012-11-07, Last modification date: 2023-12-20) |
| Primary citation | Kaan, H.Y.K.,Major, J.,Tkocz, K.,Kozielski, F.,Rosenfeld, S.S. "Snapshots" of Ispinesib-Induced Conformational Changes in the Mitotic Kinesin Eg5. J.Biol.Chem., 288:18588-, 2013 Cited by PubMed Abstract: Kinesins comprise a superfamily of molecular motors that drive a wide variety of cellular physiologies, from cytoplasmic transport to formation of the bipolar spindle in mitosis. These differing roles are reflected in corresponding polymorphisms in key kinesin structural elements. One of these is a unique loop and stem motif found in all kinesins and referred to as loop 5 (L5). This loop is longest in the mitotic kinesin Eg5 and is the target for a number of small molecule inhibitors, including ispinesib, which is being used in clinical trials in patients with cancer. In this study, we have used x-ray crystallography to identify a new structure of an Eg5-ispinesib complex and have combined this with transient state kinetics to identify a plausible sequence of conformational changes that occur in response to ispinesib binding. Our results demonstrate that ispinesib-induced structural changes in L5 from Eg5 lead to subsequent changes in the conformation of the switch II loop and helix and in the neck linker. We conclude that L5 in Eg5 simultaneously regulates the structure of both the ATP binding site and the motor's mechanical elements that generate force. PubMed: 23658017DOI: 10.1074/JBC.M113.462648 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.45 Å) |
Structure validation
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