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==MAP4K4 in complex with inhibitor (compound 22), 6-(3-CHLOROPHENYL)QUINAZOLIN-4-AMINE==
==MAP4K4 in complex with inhibitor (compound 22), 6-(3-CHLOROPHENYL)QUINAZOLIN-4-AMINE==
<StructureSection load='4obo' size='340' side='right' caption='[[4obo]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
<StructureSection load='4obo' size='340' side='right'caption='[[4obo]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4obo]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OBO OCA]. <br>
<table><tr><td colspan='2'>[[4obo]] is a 2 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=4OBO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OBO FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QV:6-(3-CHLOROPHENYL)QUINAZOLIN-4-AMINE'>2QV</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene><br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4obp|4obp]], [[4obq|4obq]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2QV:6-(3-CHLOROPHENYL)QUINAZOLIN-4-AMINE'>2QV</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></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=4obo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4obo OCA], [https://pdbe.org/4obo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4obo RCSB], [https://www.ebi.ac.uk/pdbsum/4obo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4obo ProSAT]</span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4obo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4obo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4obo RCSB], [http://www.ebi.ac.uk/pdbsum/4obo PDBsum]</span></td></tr>
</table>
<table>
== Function ==
<div style="background-color:#fffaf0;">
[https://www.uniprot.org/uniprot/M4K4_HUMAN 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.<ref>PMID:9890973</ref> <ref>PMID:21690388</ref>  
== Publication Abstract from PubMed ==
Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is a serine/threonine kinase implicated in the regulation of many biological processes. A fragment-based lead discovery approach was used to generate potent and selective MAP4K4 inhibitors. The fragment hit pursued in this article had excellent ligand efficiency (LE), an important attribute for subsequent successful optimization into drug-like lead compounds. The optimization efforts eventually led us to focus on the pyridopyrimidine series, from which 6-(2-fluoropyridin-4-yl)pyrido[3,2-d]pyrimidin-4-amine (29) was identified. This compound had low nanomolar potency, excellent kinase selectivity, and good in vivo exposure, and demonstrated in vivo pharmacodynamic effects in a human tumor xenograft model.
 
Discovery of Selective 4-Amino-pyridopyrimidine Inhibitors of MAP4K4 Using Fragment-Based Lead Identification and Optimization.,Crawford TD, Ndubaku CO, Chen H, Boggs JW, Bravo BJ, Delatorre K, Giannetti AM, Gould SE, Harris SF, Magnuson SR, McNamara E, Murray LJ, Nonomiya J, Sambrone A, Schmidt S, Smyczek T, Stanley M, Vitorino P, Wang L, West K, Wu P, Ye W J Med Chem. 2014 Apr 9. PMID:24673130<ref>PMID:24673130</ref>
 
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
</div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Homo sapiens]]
[[Category: Coons, M.]]
[[Category: Large Structures]]
[[Category: Harris, S F.]]
[[Category: Coons M]]
[[Category: Wu, P.]]
[[Category: Harris SF]]
[[Category: Kinase]]
[[Category: Wu P]]
[[Category: Transferase-transferase inhibitor complex]]

Latest revision as of 12:38, 1 March 2024

MAP4K4 in complex with inhibitor (compound 22), 6-(3-CHLOROPHENYL)QUINAZOLIN-4-AMINE

4obo, resolution 2.10Å

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