View source for 8vf6


==Crystal structure of Serine/threonine-protein kinase 33 (STK33) Kinase Domain in complex with inhibitor CDD-2211==
<StructureSection load='8vf6' size='340' side='right'caption='[[8vf6]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vf6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8VF6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VF6 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AAY:{3-[([1,1-biphenyl]-2-yl)ethynyl]-1H-indazol-5-yl}[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methanone'>A1AAY</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8vf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vf6 OCA], [https://pdbe.org/8vf6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vf6 RCSB], [https://www.ebi.ac.uk/pdbsum/8vf6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vf6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/STK33_HUMAN STK33_HUMAN] Serine/threonine protein kinase which phosphorylates VIME. May play a specific role in the dynamic behavior of the intermediate filament cytoskeleton by phosphorylation of VIME (By similarity). Not essential for the survival of KRAS-dependent AML cell lines.<ref>PMID:21742770</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Men or mice with homozygous serine/threonine kinase 33 (STK33) 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 STK33 perturbations without altering testis size. Thus, STK33 is a chemically validated, nonhormonal contraceptive target, and CDD-2807 is an effective tool compound.

Reversible male contraception by targeted inhibition of serine/threonine kinase 33.,Ku AF, Sharma KL, Ta HM, Sutton CM, Bohren KM, Wang Y, Chamakuri S, Chen R, Hakenjos JM, Jimmidi R, Kent K, Li F, Li JY, Ma L, Madasu C, Palaniappan M, Palmer SS, Qin X, Robers MB, Sankaran B, Tan Z, Vasquez YM, Wang J, Wilkinson J, Yu Z, Ye Q, Young DW, Teng M, Kim C, Matzuk MM Science. 2024 May 24;384(6698):885-890. doi: 10.1126/science.adl2688. Epub 2024 , May 23. PMID:38781365<ref>PMID:38781365</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8vf6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kim C]]
[[Category: Ku KA]]
[[Category: Matzuk MM]]
[[Category: Ta HM]]