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4x7o

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Co-crystal Structure of PERK bound to 1-[5-(4-amino-2,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydro-1H-indol-1-yl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]ethanone inhibitor

Structural highlights

4x7o is a 1 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 2.65Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

E2AK3_HUMAN Wolcott-Rallison syndrome. The disease is caused by mutations affecting the gene represented in this entry.^[1]

Function

E2AK3_HUMAN Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (By similarity).

Publication Abstract from PubMed

The structure-based design and optimization of a novel series of selective PERK inhibitors are described resulting in the identification of 44 as a potent, highly selective, and orally active tool compound suitable for PERK pathway biology exploration both in vitro and in vivo.

Discovery of 1H-Pyrazol-3(2H)-ones as Potent and Selective Inhibitors of Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK).,Smith AL, Andrews KL, Beckmann H, Bellon SF, Beltran PJ, Booker S, Chen H, Chung YA, D'Angelo ND, Dao J, Dellamaggiore KR, Jaeckel P, Kendall R, Labitzke K, Long AM, Materna-Reichelt S, Mitchell P, Norman MH, Powers D, Rose M, Shaffer PL, Wu MM, Lipford JR J Med Chem. 2015 Jan 14. PMID:25587754^[2]

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

References

↑ Delepine M, Nicolino M, Barrett T, Golamaully M, Lathrop GM, Julier C. EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. Nat Genet. 2000 Aug;25(4):406-9. PMID:10932183 doi:http://dx.doi.org/10.1038/78085
↑ Smith AL, Andrews KL, Beckmann H, Bellon SF, Beltran PJ, Booker S, Chen H, Chung YA, D'Angelo ND, Dao J, Dellamaggiore KR, Jaeckel P, Kendall R, Labitzke K, Long AM, Materna-Reichelt S, Mitchell P, Norman MH, Powers D, Rose M, Shaffer PL, Wu MM, Lipford JR. Discovery of 1H-Pyrazol-3(2H)-ones as Potent and Selective Inhibitors of Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK). J Med Chem. 2015 Jan 14. PMID:25587754 doi:http://dx.doi.org/10.1021/jm5017494

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4x7o"

Categories: Homo sapiens | Large Structures | Chen H | Long AM | Shaffer PL

@@ Line 1: / Line 1: @@
 ==Co-crystal Structure of PERK bound to 1-[5-(4-amino-2,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydro-1H-indol-1-yl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]ethanone inhibitor==
-<StructureSection load='4x7o' size='340' side='right' caption='[[4x7o]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
+<StructureSection load='4x7o' size='340' side='right'caption='[[4x7o]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4x7o]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X7O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X7O FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4x7o]] is a 1 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=4X7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X7O FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3Z6:1-[5-(4-AMINO-2,7-DIMETHYL-7H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-2,3-DIHYDRO-1H-INDOL-1-YL]-2-[3-FLUORO-5-(TRIFLUOROMETHYL)PHENYL]ETHANONE'>3Z6</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]] 2.65&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4x7j|4x7j]], [[4x7h|4x7h]], [[4x7k|4x7k]], [[4x7l|4x7l]], [[4x7n|4x7n]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3Z6:1-[5-(4-AMINO-2,7-DIMETHYL-7H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-2,3-DIHYDRO-1H-INDOL-1-YL]-2-[3-FLUORO-5-(TRIFLUOROMETHYL)PHENYL]ETHANONE'>3Z6</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=4x7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x7o OCA], [https://pdbe.org/4x7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x7o RCSB], [https://www.ebi.ac.uk/pdbsum/4x7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x7o ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4x7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x7o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4x7o RCSB], [http://www.ebi.ac.uk/pdbsum/4x7o PDBsum]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/E2AK3_HUMAN E2AK3_HUMAN]] Wolcott-Rallison syndrome. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:10932183</ref>
+[https://www.uniprot.org/uniprot/E2AK3_HUMAN E2AK3_HUMAN] Wolcott-Rallison syndrome. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:10932183</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/E2AK3_HUMAN E2AK3_HUMAN]] Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (By similarity).
+[https://www.uniprot.org/uniprot/E2AK3_HUMAN E2AK3_HUMAN] Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (By similarity).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4x7o" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Homo sapiens]]
-[[Category: Chen, H]]
+[[Category: Large Structures]]
-[[Category: Long, A M]]
+[[Category: Chen H]]
-[[Category: Shaffer, P L]]
+[[Category: Long AM]]
-[[Category: Catalytic domain]]
+[[Category: Shaffer PL]]
-[[Category: Complex]]
-[[Category: Transferase-transferase inhibitor]]
-[[Category: Transferase-transferase inhibitor complex]]

4x7o

From Proteopedia

Current revision

Co-crystal Structure of PERK bound to 1-[5-(4-amino-2,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydro-1H-indol-1-yl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]ethanone inhibitor

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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