This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4obp

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 05:03, 5 August 2016

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

Structural highlights

4obp 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:	4obo, 4obq
Gene:	HGK, KIAA0687, MAP4K4, 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

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^[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
↑ 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. Discovery of Selective 4-Amino-pyridopyrimidine Inhibitors of MAP4K4 Using Fragment-Based Lead Identification and Optimization. J Med Chem. 2014 Apr 9. PMID:24673130 doi:http://dx.doi.org/10.1021/jm500155b

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/4obp"

@@ Line 1: / Line 1: @@
 ==MAP4K4 in complex with inhibitor (compound 29), 6-(2-FLUOROPYRIDIN-4-YL)PYRIDO[3,2-D]PYRIMIDIN-4-AMINE==
 <StructureSection load='4obp' size='340' side='right' caption='[[4obp]], [[Resolution|resolution]] 2.27&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HGK, KIAA0687, MAP4K4, 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=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>
+<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=4obp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4obp OCA], [http://pdbe.org/4obp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4obp RCSB], [http://www.ebi.ac.uk/pdbsum/4obp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4obp ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4obp" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4obp

From Proteopedia

Revision as of 05:03, 5 August 2016

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox