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8eq9

From Proteopedia

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Current revision

Co-crystal structure of PERK with compound 11

Structural highlights

8eq9 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 2.86Å
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 protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is one of three endoplasmic reticulum (ER) transmembrane sensors of the unfolded protein response (UPR) responsible for regulating protein synthesis and alleviating ER stress. PERK has been implicated in tumorigenesis, cancer cell survival as well metabolic diseases such as diabetes. The structure-based design and optimization of a novel mandelamide-derived pyrrolopyrimidine series of PERK inhibitors as described herein, resulted in the identification of compound 26, a potent, selective, and orally bioavailable compound suitable for interrogating PERK pathway biology in vitro and in vivo, with pharmacokinetics suitable for once-a-day oral dosing in mice.

Optimization of a Novel Mandelamide-Derived Pyrrolopyrimidine Series of PERK Inhibitors.,Stokes ME, Surman MD, Calvo V, Surguladze D, Li AH, Gasparek J, Betzenhauser M, Zhu G, Du H, Rigby AC, Mulvihill MJ Pharmaceutics. 2022 Oct 19;14(10):2233. doi: 10.3390/pharmaceutics14102233. PMID:36297668^[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
↑ Stokes ME, Surman MD, Calvo V, Surguladze D, Li AH, Gasparek J, Betzenhauser M, Zhu G, Du H, Rigby AC, Mulvihill MJ. Optimization of a Novel Mandelamide-Derived Pyrrolopyrimidine Series of PERK Inhibitors. Pharmaceutics. 2022 Oct 19;14(10):2233. doi: 10.3390/pharmaceutics14102233. PMID:36297668 doi:http://dx.doi.org/10.3390/pharmaceutics14102233

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/8eq9"

Categories: Homo sapiens | Large Structures | Mulvihill MJ | Surman MD | Zhu G

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[8eq9]] 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=8EQ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EQ9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=WPB:(2R)-N-[(4M)-4-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-3-methylphenyl]-2-(3-fluorophenyl)-2-hydroxyacetamide'>WPB</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]] 2.86&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=WPB:(2R)-N-[(4M)-4-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-3-methylphenyl]-2-(3-fluorophenyl)-2-hydroxyacetamide'>WPB</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=8eq9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8eq9 OCA], [https://pdbe.org/8eq9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8eq9 RCSB], [https://www.ebi.ac.uk/pdbsum/8eq9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8eq9 ProSAT]</span></td></tr>
 </table>

8eq9

From Proteopedia

Current revision

Co-crystal structure of PERK with compound 11

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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