8VF6
Crystal structure of Serine/threonine-protein kinase 33 (STK33) Kinase Domain in complex with inhibitor CDD-2211
This is a non-PDB format compatible entry.
Summary for 8VF6
| Entry DOI | 10.2210/pdb8vf6/pdb |
| Descriptor | Serine/threonine-protein kinase 33, {3-[([1,1'-biphenyl]-2-yl)ethynyl]-1H-indazol-5-yl}[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methanone (3 entities in total) |
| Functional Keywords | kinase, stk33, cytosolic protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 65938.19 |
| Authors | |
| Primary citation | Ku, A.F.,Sharma, K.L.,Ta, H.M.,Sutton, C.M.,Bohren, K.M.,Wang, Y.,Chamakuri, S.,Chen, R.,Hakenjos, J.M.,Jimmidi, R.,Kent, K.,Li, F.,Li, J.Y.,Ma, L.,Madasu, C.,Palaniappan, M.,Palmer, S.S.,Qin, X.,Robers, M.B.,Sankaran, B.,Tan, Z.,Vasquez, Y.M.,Wang, J.,Wilkinson, J.,Yu, Z.,Ye, Q.,Young, D.W.,Teng, M.,Kim, C.,Matzuk, M.M. Reversible male contraception by targeted inhibition of serine/threonine kinase 33. Science, 384:885-890, 2024 Cited by PubMed Abstract: Men or mice with homozygous serine/threonine kinase 33 () mutations are sterile owing to defective sperm morphology and motility. To chemically evaluate STK33 for male contraception with STK33-specific inhibitors, we screened our multibillion-compound collection of DNA-encoded chemical libraries, uncovered potent STK33-specific inhibitors, determined the STK33 kinase domain structure bound with a truncated hit CDD-2211, and generated an optimized hit CDD-2807 that demonstrates nanomolar cellular potency (half-maximal inhibitory concentration = 9.2 nanomolar) and favorable metabolic stability. In mice, CDD-2807 exhibited no toxicity, efficiently crossed the blood-testis barrier, did not accumulate in brain, and induced a reversible contraceptive effect that phenocopied genetic perturbations without altering testis size. Thus, STK33 is a chemically validated, nonhormonal contraceptive target, and CDD-2807 is an effective tool compound. PubMed: 38781365DOI: 10.1126/science.adl2688 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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