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5cen

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Revision as of 11:35, 27 March 2020

Crystal structure of DLK (kinase domain)

Structural highlights

5cen 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.
Related:	5ceo, 5cep, 5ceq
Gene:	MAP3K12, ZPK (HUMAN)
Activity:	Mitogen-activated protein kinase kinase kinase, with EC number 2.7.11.25
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[M3K12_HUMAN] May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.

Publication Abstract from PubMed

Recent data suggest that inhibition of dual leucine zipper kinase (DLK, MAP3K12) has therapeutic potential for treatment of a number of indications ranging from acute neuronal injury to chronic neurodegenerative disease. Thus, high demand exists for selective small molecule DLK inhibitors with favorable drug-like properties and good CNS penetration. Herein we describe a shape-based scaffold hopping approach to convert pyrimidine 1 to a pyrazole core with improved physicochemical properties. We also present the first crystal structures of DLK. By utilizing a combination of property and structure-based design, we identified inhibitor 11, a potent, selective, and brain-penetrant inhibitor of DLK with activity in an in vivo nerve injury model.

Scaffold-Hopping and Structure-Based Discovery of Potent, Selective, And Brain Penetrant N-(1H-Pyrazol-3-yl)pyridin-2-amine Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12).,Patel S, Harris SF, Gibbons P, Deshmukh G, Gustafson A, Kellar T, Lin H, Liu X, Liu Y, Liu Y, Ma C, Scearce-Levie K, Ghosh AS, Shin YG, Solanoy H, Wang J, Wang B, Yin J, Siu M, Lewcock JW J Med Chem. 2015 Oct 2. PMID:26431428^[1]

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

References

↑ Patel S, Harris SF, Gibbons P, Deshmukh G, Gustafson A, Kellar T, Lin H, Liu X, Liu Y, Liu Y, Ma C, Scearce-Levie K, Ghosh AS, Shin YG, Solanoy H, Wang J, Wang B, Yin J, Siu M, Lewcock JW. Scaffold-Hopping and Structure-Based Discovery of Potent, Selective, And Brain Penetrant N-(1H-Pyrazol-3-yl)pyridin-2-amine Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12). J Med Chem. 2015 Oct 2. PMID:26431428 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b01072

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5cen"

@@ Line 1: / Line 1: @@
 ==Crystal structure of DLK (kinase domain)==
-<StructureSection load='5cen' size='340' side='right' caption='[[5cen]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+<StructureSection load='5cen' size='340' side='right'caption='[[5cen]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5cen]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CEN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CEN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5cen]] 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=5CEN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CEN FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ceo|5ceo]], [[5cep|5cep]], [[5ceq|5ceq]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAP3K12, ZPK ([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/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </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=5cen FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cen OCA], [http://pdbe.org/5cen PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cen RCSB], [http://www.ebi.ac.uk/pdbsum/5cen PDBsum]</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=5cen FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cen OCA], [http://pdbe.org/5cen PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cen RCSB], [http://www.ebi.ac.uk/pdbsum/5cen PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cen ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Mitogen-activated protein kinase kinase kinase]]
 [[Category: HARRIS, S F]]

5cen

From Proteopedia

Revision as of 11:35, 27 March 2020

Crystal structure of DLK (kinase domain)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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