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5di1

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Revision as of 08:04, 8 April 2020

MAP4K4 in complex with an inhibitor

Structural highlights

5di1 is a 2 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:	4zp5
Gene:	MAP4K4, HGK, KIAA0687, NIK (HUMAN)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[M4K4_HUMAN] Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322.^[1] ^[2]

Publication Abstract from PubMed

Recent studies in adipose tissue, pancreas, muscle, and macrophages suggest that MAP4K4, a serine/threonine protein kinase may be a viable target for antidiabetic drugs. As part of the evaluation of MAP4K4 as a novel antidiabetic target, a tool compound, 16 (PF-6260933) and a lead 17 possessing excellent kinome selectivity and suitable properties were delivered to establish proof of concept in vivo. The medicinal chemistry effort that led to the discovery of these lead compounds is described herein together with in vivo pharmacokinetic properties and activity in a model of insulin resistance.

Discovery of an in Vivo Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment.,Ammirati M, Bagley SW, Bhattacharya SK, Buckbinder L, Carlo AA, Conrad R, Cortes C, Dow RL, Dowling MS, El-Kattan A, Ford K, Guimaraes CR, Hepworth D, Jiao W, LaPerle J, Liu S, Londregan A, Loria PM, Mathiowetz AM, Munchhof M, Orr ST, Petersen DN, Price DA, Skoura A, Smith AC, Wang J ACS Med Chem Lett. 2015 Oct 6;6(11):1128-33. doi: 10.1021/acsmedchemlett.5b00215., eCollection 2015 Nov 12. PMID:26617966^[3]

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

References

↑ Yao Z, Zhou G, Wang XS, Brown A, Diener K, Gan H, Tan TH. A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway. J Biol Chem. 1999 Jan 22;274(4):2118-25. PMID:9890973
↑ Kaneko S, Chen X, Lu P, Yao X, Wright TG, Rajurkar M, Kariya K, Mao J, Ip YT, Xu L. Smad inhibition by the Ste20 kinase Misshapen. Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11127-32. doi:, 10.1073/pnas.1104128108. Epub 2011 Jun 20. PMID:21690388 doi:http://dx.doi.org/10.1073/pnas.1104128108
↑ Ammirati M, Bagley SW, Bhattacharya SK, Buckbinder L, Carlo AA, Conrad R, Cortes C, Dow RL, Dowling MS, El-Kattan A, Ford K, Guimaraes CR, Hepworth D, Jiao W, LaPerle J, Liu S, Londregan A, Loria PM, Mathiowetz AM, Munchhof M, Orr ST, Petersen DN, Price DA, Skoura A, Smith AC, Wang J. Discovery of an in Vivo Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment. ACS Med Chem Lett. 2015 Oct 6;6(11):1128-33. doi: 10.1021/acsmedchemlett.5b00215., eCollection 2015 Nov 12. PMID:26617966 doi:http://dx.doi.org/10.1021/acsmedchemlett.5b00215

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/5di1"

@@ Line 1: / Line 1: @@
 ==MAP4K4 in complex with an inhibitor==
-<StructureSection load='5di1' size='340' side='right' caption='[[5di1]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+<StructureSection load='5di1' size='340' side='right'caption='[[5di1]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5di1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DI1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DI1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5di1]] is a 2 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=5DI1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DI1 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5DF:4-{6-AMINO-5-[4-(METHYLSULFONYL)PHENYL]PYRIDIN-3-YL}PHENOL'>5DF</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5DF:4-{6-AMINO-5-[4-(METHYLSULFONYL)PHENYL]PYRIDIN-3-YL}PHENOL'>5DF</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zp5|4zp5]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAP4K4, HGK, KIAA0687, NIK ([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=5di1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5di1 OCA], [http://pdbe.org/5di1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5di1 RCSB], [http://www.ebi.ac.uk/pdbsum/5di1 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5di1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5di1 OCA], [http://pdbe.org/5di1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5di1 RCSB], [http://www.ebi.ac.uk/pdbsum/5di1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5di1 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 23: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Liu, S]]

5di1

From Proteopedia

Revision as of 08:04, 8 April 2020

MAP4K4 in complex with an inhibitor

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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