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4x7n

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Revision as of 06:58, 29 May 2019

Co-crystal Structure of PERK bound to 4-[2-amino-4-methyl-3-(2-methylquinolin-6-yl)benzoyl]-1-methyl-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one inhibitor

Structural highlights

4x7n is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4x7j, 4x7h, 4x7k, 4x7l, 4x7o
Gene:	EIF2AK3, PEK, PERK (HUMAN)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
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/4x7n"

@@ Line 1: / Line 1: @@
 ==Co-crystal Structure of PERK bound to 4-[2-amino-4-methyl-3-(2-methylquinolin-6-yl)benzoyl]-1-methyl-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one inhibitor==
-<StructureSection load='4x7n' size='340' side='right' caption='[[4x7n]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
+<StructureSection load='4x7n' size='340' side='right'caption='[[4x7n]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4x7n]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X7N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X7N FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4x7n]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X7N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X7N FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3Z5:4-[2-AMINO-4-METHYL-3-(2-METHYLQUINOLIN-6-YL)BENZOYL]-1-METHYL-2,5-DIPHENYL-1,2-DIHYDRO-3H-PYRAZOL-3-ONE'>3Z5</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></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]], [[4x7o|4x7o]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EIF2AK3, PEK, PERK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4x7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x7n OCA], [http://pdbe.org/4x7n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x7n RCSB], [http://www.ebi.ac.uk/pdbsum/4x7n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x7n ProSAT]</span></td></tr>
@@ Line 26: / Line 27: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Chen, H]]
@@ Line 33: / Line 36: @@
 [[Category: Complex]]
 [[Category: Transferase-transferase inhibitor]]
+[[Category: Transferase-transferase inhibitor complex]]

4x7n

From Proteopedia

Revision as of 06:58, 29 May 2019

Co-crystal Structure of PERK bound to 4-[2-amino-4-methyl-3-(2-methylquinolin-6-yl)benzoyl]-1-methyl-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one inhibitor

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

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