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4obp

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==MAP4K4 in complex with inhibitor (compound 29), 6-(2-FLUOROPYRIDIN-4-YL)PYRIDO[3,2-D]PYRIMIDIN-4-AMINE==
==MAP4K4 in complex with inhibitor (compound 29), 6-(2-FLUOROPYRIDIN-4-YL)PYRIDO[3,2-D]PYRIMIDIN-4-AMINE==
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<StructureSection load='4obp' size='340' side='right' caption='[[4obp]], [[Resolution|resolution]] 2.27&Aring;' scene=''>
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<StructureSection load='4obp' size='340' side='right'caption='[[4obp]], [[Resolution|resolution]] 2.27&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4obp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OBP OCA]. <br>
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<table><tr><td colspan='2'>[[4obp]] 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=4OBP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OBP FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QU:6-(2-FLUOROPYRIDIN-4-YL)PYRIDO[3,2-D]PYRIMIDIN-4-AMINE'>2QU</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.27&#8491;</td></tr>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4obo|4obo]], [[4obq|4obq]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2QU:6-(2-FLUOROPYRIDIN-4-YL)PYRIDO[3,2-D]PYRIMIDIN-4-AMINE'>2QU</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4obp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4obp OCA], [https://pdbe.org/4obp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4obp RCSB], [https://www.ebi.ac.uk/pdbsum/4obp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4obp ProSAT]</span></td></tr>
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<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=4obp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4obp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4obp RCSB], [http://www.ebi.ac.uk/pdbsum/4obp PDBsum]</span></td></tr>
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</table>
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<table>
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== Function ==
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<div style="background-color:#fffaf0;">
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[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>
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== Publication Abstract from PubMed ==
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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.
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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>
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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</div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Homo sapiens]]
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[[Category: Harris, S F.]]
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[[Category: Large Structures]]
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[[Category: Wu, P.]]
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[[Category: Harris SF]]
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[[Category: Kinase]]
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[[Category: Wu P]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

MAP4K4 in complex with inhibitor (compound 29), 6-(2-FLUOROPYRIDIN-4-YL)PYRIDO[3,2-D]PYRIMIDIN-4-AMINE

PDB ID 4obp

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