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4ykn

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Revision as of 09:40, 22 November 2017

Pi3K alpha lipid kinase with Active Site Inhibitor

Structural highlights

4ykn is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	PIK3CA (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[P85A_HUMAN] Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling.^[1] ^[2] ^[3]

Publication Abstract from PubMed

In the search of PI3K p110alpha wild type and H1047R mutant selective small molecule leads, an encoded library technology (ELT) campaign against the desired target proteins was performed which led to the discovery of a selective chemotype for PI3K isoforms from a three-cycle DNA encoded library. An X-ray crystal structure of a representative inhibitor from this chemotype demonstrated a unique binding mode in the p110alpha protein.

Discovery of a Potent Class of PI3Kalpha Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT).,Yang H, Medeiros PF, Raha K, Elkins P, Lind KE, Lehr R, Adams ND, Burgess JL, Schmidt SJ, Knight SD, Auger KR, Schaber MD, Franklin GJ, Ding Y, DeLorey JL, Centrella PA, Mataruse S, Skinner SR, Clark MA, Cuozzo JW, Evindar G ACS Med Chem Lett. 2015 Mar 20;6(5):531-6. doi: 10.1021/acsmedchemlett.5b00025., eCollection 2015 May 14. PMID:26005528^[4]

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

References

↑ Vainikka S, Joukov V, Wennstrom S, Bergman M, Pelicci PG, Alitalo K. Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison with FGFR-1. J Biol Chem. 1994 Jul 15;269(28):18320-6. PMID:7518429
↑ Miled N, Yan Y, Hon WC, Perisic O, Zvelebil M, Inbar Y, Schneidman-Duhovny D, Wolfson HJ, Backer JM, Williams RL. Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science. 2007 Jul 13;317(5835):239-42. PMID:17626883 doi:317/5835/239
↑ Mandelker D, Gabelli SB, Schmidt-Kittler O, Zhu J, Cheong I, Huang CH, Kinzler KW, Vogelstein B, Amzel LM. A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane. Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):16996-7001. Epub 2009 Sep 23. PMID:19805105
↑ Yang H, Medeiros PF, Raha K, Elkins P, Lind KE, Lehr R, Adams ND, Burgess JL, Schmidt SJ, Knight SD, Auger KR, Schaber MD, Franklin GJ, Ding Y, DeLorey JL, Centrella PA, Mataruse S, Skinner SR, Clark MA, Cuozzo JW, Evindar G. Discovery of a Potent Class of PI3Kalpha Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT). ACS Med Chem Lett. 2015 Mar 20;6(5):531-6. doi: 10.1021/acsmedchemlett.5b00025., eCollection 2015 May 14. PMID:26005528 doi:http://dx.doi.org/10.1021/acsmedchemlett.5b00025

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/4ykn"

@@ Line 3: / Line 3: @@
 <StructureSection load='4ykn' size='340' side='right' caption='[[4ykn]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4ykn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YKN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YKN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4ykn]] is a 1 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=4YKN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YKN FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4EL:3-(6-METHOXYPYRIDIN-3-YL)-5-[({4-[(5-METHYL-1,3,4-THIADIAZOL-2-YL)SULFAMOYL]PHENYL}AMINO)METHYL]BENZOIC+ACID'>4EL</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PIK3CA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4ykn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ykn OCA], [http://pdbe.org/4ykn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ykn RCSB], [http://www.ebi.ac.uk/pdbsum/4ykn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ykn ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Elkins, P A]]
 [[Category: Lipid kinase]]

4ykn

From Proteopedia

Revision as of 09:40, 22 November 2017

Pi3K alpha lipid kinase with Active Site Inhibitor

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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