5x5o

From Proteopedia

(Difference between revisions)

Revision as of 08:30, 27 December 2017

Crystal structure of ZAK in complex with compound D2829

Structural highlights

5x5o is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:	Mitogen-activated protein kinase kinase kinase, with EC number 2.7.11.25
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MLTK_HUMAN] Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2. Isoform 1, but not isoform 2, causes cell shrinkage and disruption of actin stress fibers. Isoform 1 may have role in neoplastic cell transformation and cancer development. Isoform 1, but not isoform 2, phosphorylates histone H3 at 'Ser-28'.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

A series of N-(3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)benzenesulfonamides were designed as the first class of highly selective ZAK inhibitors. The representative compound 3h strongly inhibits the kinase activity of ZAK with an IC50 of 3.3 nM and dose-dependently suppresses the activation of ZAK downstream signals in vitro and in vivo, while it is significantly less potent for the majority of 403 nonmutated kinases evaluated. Compound 3h also exhibits orally therapeutic effects on cardiac hypertrophy in a spontaneous hypertensive rat model.

Structure Based Design of N-(3-((1H-Pyrazolo[3,4-b]pyridin-5-yl)ethynyl)benzenesulfonamides as Selective Leucine-Zipper and Sterile-alpha Motif Kinase (ZAK) Inhibitors.,Chang Y, Lu X, Shibu MA, Dai YB, Luo J, Zhang Y, Li Y, Zhao P, Zhang Z, Xu Y, Tu ZC, Zhang QW, Yun CH, Huang CY, Ding K J Med Chem. 2017 Jul 13;60(13):5927-5932. doi: 10.1021/acs.jmedchem.7b00572. Epub, 2017 Jun 16. PMID:28586211^[7]

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

References

↑ Liu TC, Huang CJ, Chu YC, Wei CC, Chou CC, Chou MY, Chou CK, Yang JJ. Cloning and expression of ZAK, a mixed lineage kinase-like protein containing a leucine-zipper and a sterile-alpha motif. Biochem Biophys Res Commun. 2000 Aug 11;274(3):811-6. PMID:10924358 doi:http://dx.doi.org/10.1006/bbrc.2000.3236
↑ Gotoh I, Adachi M, Nishida E. Identification and characterization of a novel MAP kinase kinase kinase, MLTK. J Biol Chem. 2001 Feb 9;276(6):4276-86. Epub 2000 Oct 19. PMID:11042189 doi:http://dx.doi.org/10.1074/jbc.M008595200
↑ Gross EA, Callow MG, Waldbaum L, Thomas S, Ruggieri R. MRK, a mixed lineage kinase-related molecule that plays a role in gamma-radiation-induced cell cycle arrest. J Biol Chem. 2002 Apr 19;277(16):13873-82. Epub 2002 Feb 8. PMID:11836244 doi:http://dx.doi.org/10.1074/jbc.M111994200
↑ Cho YY, Bode AM, Mizuno H, Choi BY, Choi HS, Dong Z. A novel role for mixed-lineage kinase-like mitogen-activated protein triple kinase alpha in neoplastic cell transformation and tumor development. Cancer Res. 2004 Jun 1;64(11):3855-64. PMID:15172994 doi:http://dx.doi.org/10.1158/0008-5472.CAN-04-0201
↑ Tosti E, Waldbaum L, Warshaw G, Gross EA, Ruggieri R. The stress kinase MRK contributes to regulation of DNA damage checkpoints through a p38gamma-independent pathway. J Biol Chem. 2004 Nov 12;279(46):47652-60. Epub 2004 Sep 1. PMID:15342622 doi:http://dx.doi.org/10.1074/jbc.M409961200
↑ Choi HS, Choi BY, Cho YY, Zhu F, Bode AM, Dong Z. Phosphorylation of Ser28 in histone H3 mediated by mixed lineage kinase-like mitogen-activated protein triple kinase alpha. J Biol Chem. 2005 Apr 8;280(14):13545-53. Epub 2005 Jan 31. PMID:15684425 doi:http://dx.doi.org/M410521200
↑ Chang Y, Lu X, Shibu MA, Dai YB, Luo J, Zhang Y, Li Y, Zhao P, Zhang Z, Xu Y, Tu ZC, Zhang QW, Yun CH, Huang CY, Ding K. Structure Based Design of N-(3-((1H-Pyrazolo[3,4-b]pyridin-5-yl)ethynyl)benzenesulfonamides as Selective Leucine-Zipper and Sterile-alpha Motif Kinase (ZAK) Inhibitors. J Med Chem. 2017 Jul 13;60(13):5927-5932. doi: 10.1021/acs.jmedchem.7b00572. Epub, 2017 Jun 16. PMID:28586211 doi:http://dx.doi.org/10.1021/acs.jmedchem.7b00572

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/5x5o"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5x5o is ON HOLD  until Paper Publication
+==Crystal structure of ZAK in complex with compound D2829==
+<StructureSection load='5x5o' size='340' side='right' caption='[[5x5o]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5x5o]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X5O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X5O FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7Z0:N-[2,4-bis(fluoranyl)-3-[2-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]phenyl]-3-bromanyl-benzenesulfonamide'>7Z0</scene></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=5x5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x5o OCA], [http://pdbe.org/5x5o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x5o RCSB], [http://www.ebi.ac.uk/pdbsum/5x5o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x5o ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/MLTK_HUMAN MLTK_HUMAN]] Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2. Isoform 1, but not isoform 2, causes cell shrinkage and disruption of actin stress fibers. Isoform 1 may have role in neoplastic cell transformation and cancer development. Isoform 1, but not isoform 2, phosphorylates histone H3 at 'Ser-28'.<ref>PMID:10924358</ref> <ref>PMID:11042189</ref> <ref>PMID:11836244</ref> <ref>PMID:15172994</ref> <ref>PMID:15342622</ref> <ref>PMID:15684425</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A series of N-(3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)benzenesulfonamides were designed as the first class of highly selective ZAK inhibitors. The representative compound 3h strongly inhibits the kinase activity of ZAK with an IC50 of 3.3 nM and dose-dependently suppresses the activation of ZAK downstream signals in vitro and in vivo, while it is significantly less potent for the majority of 403 nonmutated kinases evaluated. Compound 3h also exhibits orally therapeutic effects on cardiac hypertrophy in a spontaneous hypertensive rat model.
-Authors: Dai, Y.B., Zhao, P., Yun, C.H.
+Structure Based Design of N-(3-((1H-Pyrazolo[3,4-b]pyridin-5-yl)ethynyl)benzenesulfonamides as Selective Leucine-Zipper and Sterile-alpha Motif Kinase (ZAK) Inhibitors.,Chang Y, Lu X, Shibu MA, Dai YB, Luo J, Zhang Y, Li Y, Zhao P, Zhang Z, Xu Y, Tu ZC, Zhang QW, Yun CH, Huang CY, Ding K J Med Chem. 2017 Jul 13;60(13):5927-5932. doi: 10.1021/acs.jmedchem.7b00572. Epub, 2017 Jun 16. PMID:28586211<ref>PMID:28586211</ref>
-Description: Crystal structure of ZAK in complex with compound D2829
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5x5o" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Mitogen-activated protein kinase kinase kinase]]
+[[Category: Dai, Y B]]
+[[Category: Yun, C H]]
 [[Category: Zhao, P]]
-[[Category: Dai, Y.B]]
+[[Category: Inhibitor]]
-[[Category: Yun, C.H]]
+[[Category: Kinase]]
+[[Category: Transferase]]
+[[Category: Zak]]

5x5o

From Proteopedia

Revision as of 08:30, 27 December 2017

Crystal structure of ZAK in complex with compound D2829

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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