7que

From Proteopedia

(Difference between revisions)

Current revision

The STK17A (DRAK1) Kinase Domain Bound to CKJB68

Structural highlights

7que is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ST17A_HUMAN Acts as a positive regulator of apoptosis. Also acts as a regulator of cellular reactive oxygen species.^[1] ^[2]

Publication Abstract from PubMed

Serine/threonine kinase 17A (death-associated protein kinase-related apoptosis-inducing protein kinase 1 horizontal line DRAK1) is a part of the death-associated protein kinase (DAPK) family and belongs to the so-called dark kinome. Thus, the current state of knowledge of the cellular function of DRAK1 and its involvement in pathophysiological processes is very limited. Recently, DRAK1 has been implicated in tumorigenesis of glioblastoma multiforme (GBM) and other cancers, but no selective inhibitors of DRAK1 are available yet. To this end, we optimized a pyrazolo[1,5-a]pyrimidine-based macrocyclic scaffold. Structure-guided optimization of this macrocyclic scaffold led to the development of CK156 (34), which displayed high in vitro potency (KD = 21 nM) and selectivity in kinomewide screens. Crystal structures demonstrated that CK156 (34) acts as a type I inhibitor. However, contrary to studies using genetic knockdown of DRAK1, we have seen the inhibition of cell growth of glioma cells in 2D and 3D culture only at low micromolar concentrations.

Illuminating the Dark: Highly Selective Inhibition of Serine/Threonine Kinase 17A with Pyrazolo[1,5-a]pyrimidine-Based Macrocycles.,Kurz CG, Preuss F, Tjaden A, Cusack M, Amrhein JA, Chatterjee D, Mathea S, Berger LM, Berger BT, Kramer A, Weller M, Weiss T, Muller S, Knapp S, Hanke T J Med Chem. 2022 Jun 9;65(11):7799-7817. doi: 10.1021/acs.jmedchem.2c00173. Epub , 2022 May 24. PMID:35608370^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mao P, Hever MP, Niemaszyk LM, Haghkerdar JM, Yanco EG, Desai D, Beyrouthy MJ, Kerley-Hamilton JS, Freemantle SJ, Spinella MJ. Serine/threonine kinase 17A is a novel p53 target gene and modulator of cisplatin toxicity and reactive oxygen species in testicular cancer cells. J Biol Chem. 2011 Jun 3;286(22):19381-91. doi: 10.1074/jbc.M111.218040. Epub 2011, Apr 13. PMID:21489989 doi:http://dx.doi.org/10.1074/jbc.M111.218040
↑ Sanjo H, Kawai T, Akira S. DRAKs, novel serine/threonine kinases related to death-associated protein kinase that trigger apoptosis. J Biol Chem. 1998 Oct 30;273(44):29066-71. PMID:9786912
↑ Kurz CG, Preuss F, Tjaden A, Cusack M, Amrhein JA, Chatterjee D, Mathea S, Berger LM, Berger BT, Kramer A, Weller M, Weiss T, Muller S, Knapp S, Hanke T. Illuminating the Dark: Highly Selective Inhibition of Serine/Threonine Kinase 17A with Pyrazolo[1,5-a]pyrimidine-Based Macrocycles. J Med Chem. 2022 Jun 9;65(11):7799-7817. doi: 10.1021/acs.jmedchem.2c00173. Epub , 2022 May 24. PMID:35608370 doi:http://dx.doi.org/10.1021/acs.jmedchem.2c00173

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7que"

@@ Line 3: / Line 3: @@
 <StructureSection load='7que' size='340' side='right'caption='[[7que]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7que]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QUE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7que]] 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=7QUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QUE FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F7I:~{N}-(phenylmethyl)-7,10-dioxa-13,17,18,21-tetrazatetracyclo[12.5.2.1^{2,6}.0^{17,20}]docosa-1(20),2(22),3,5,14(21),15,18-heptaene-5-carboxamide'>F7I</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F7I:~{N}-(phenylmethyl)-7,10-dioxa-13,17,18,21-tetrazatetracyclo[12.5.2.1^{2,6}.0^{17,20}]docosa-1(20),2(22),3,5,14(21),15,18-heptaene-5-carboxamide'>F7I</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=7que FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7que OCA], [https://pdbe.org/7que PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7que RCSB], [https://www.ebi.ac.uk/pdbsum/7que PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7que ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/ST17A_HUMAN ST17A_HUMAN]] Acts as a positive regulator of apoptosis. Also acts as a regulator of cellular reactive oxygen species.<ref>PMID:21489989</ref> <ref>PMID:9786912</ref>
+[https://www.uniprot.org/uniprot/ST17A_HUMAN ST17A_HUMAN] Acts as a positive regulator of apoptosis. Also acts as a regulator of cellular reactive oxygen species.<ref>PMID:21489989</ref> <ref>PMID:9786912</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Amrhein JA]]
-[[Category: Amrhein, J A]]
+[[Category: Chatterjee D]]
-[[Category: Chatterjee, D]]
+[[Category: Dederer V]]
-[[Category: Dederer, V]]
+[[Category: Hanke T]]
-[[Category: Hanke, T]]
+[[Category: Knapp S]]
-[[Category: Knapp, S]]
+[[Category: Kurz CG]]
-[[Category: Kurz, C G]]
+[[Category: Mathea S]]
-[[Category: Mathea, S]]
+[[Category: Preuss F]]
-[[Category: Preuss, F]]
-[[Category: Kinase small-molecule binder inhibitor macrocycle]]
-[[Category: Transferase]]

7que

From Proteopedia

Current revision

The STK17A (DRAK1) Kinase Domain Bound to CKJB68

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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