4oys

From Proteopedia

(Difference between revisions)

Revision as of 12:32, 1 February 2023

CRYSTAL STRUCTURE OF VPS34 IN COMPLEX WITH SAR405.

Structural highlights

4oys is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PK3C3_HUMAN Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate which plays a key role in initiation and maturation of autophagosomes. Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for the abcission step in cytokinesis. Required for transport from early to late endosomes.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Vps34 is a phosphoinositide 3-kinase (PI3K) class III isoform that has attracted major attention over the recent years because of its role in autophagy. Herein we describe the biological characterization of SAR405, which is a low-molecular-mass kinase inhibitor of Vps34 (KD 1.5 nM). This compound has an exquisite protein and lipid kinase selectivity profile that is explained by its unique binding mode and molecular interactions within the ATP binding cleft of human Vps34. To the best of our knowledge, this is the first potent and specific Vps34 inhibitor described so far. Our results demonstrate that inhibition of Vps34 kinase activity by SAR405 affects both late endosome-lysosome compartments and prevents autophagy. Moreover, we show that the concomitant inhibition of Vps34 and mTOR, with SAR405 and the US Food and Drug Administration-approved mTOR inhibitor everolimus, results in synergistic antiproliferative activity in renal tumor cell lines, indicating a potential clinical application in cancer.

A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy.,Ronan B, Flamand O, Vescovi L, Dureuil C, Durand L, Fassy F, Bachelot MF, Lamberton A, Mathieu M, Bertrand T, Marquette JP, El-Ahmad Y, Filoche-Romme B, Schio L, Garcia-Echeverria C, Goulaouic H, Pasquier B Nat Chem Biol. 2014 Dec;10(12):1013-9. doi: 10.1038/nchembio.1681. Epub 2014 Oct , 19. PMID:25326666^[4]

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

References

↑ Volinia S, Dhand R, Vanhaesebroeck B, MacDougall LK, Stein R, Zvelebil MJ, Domin J, Panaretou C, Waterfield MD. A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system. EMBO J. 1995 Jul 17;14(14):3339-48. PMID:7628435
↑ Stein MP, Feng Y, Cooper KL, Welford AM, Wandinger-Ness A. Human VPS34 and p150 are Rab7 interacting partners. Traffic. 2003 Nov;4(11):754-71. PMID:14617358
↑ Sagona AP, Nezis IP, Pedersen NM, Liestol K, Poulton J, Rusten TE, Skotheim RI, Raiborg C, Stenmark H. PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody. Nat Cell Biol. 2010 Apr;12(4):362-71. doi: 10.1038/ncb2036. Epub 2010 Mar 7. PMID:20208530 doi:http://dx.doi.org/10.1038/ncb2036
↑ Ronan B, Flamand O, Vescovi L, Dureuil C, Durand L, Fassy F, Bachelot MF, Lamberton A, Mathieu M, Bertrand T, Marquette JP, El-Ahmad Y, Filoche-Romme B, Schio L, Garcia-Echeverria C, Goulaouic H, Pasquier B. A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat Chem Biol. 2014 Dec;10(12):1013-9. doi: 10.1038/nchembio.1681. Epub 2014 Oct , 19. PMID:25326666 doi:http://dx.doi.org/10.1038/nchembio.1681

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4oys"

Categories: Homo sapiens | Large Structures | Marquette Jp | Mathieu M

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF VPS34 IN COMPLEX WITH SAR405.==
-<StructureSection load='4oys' size='340' side='right' caption='[[4oys]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+<StructureSection load='4oys' size='340' side='right'caption='[[4oys]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4oys]] 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=4OYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OYS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4oys]] is a 1 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=4OYS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OYS FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1TT:(8S)-9-[(5-CHLORANYLPYRIDIN-3-YL)METHYL]-2-[(3R)-3-METHYLMORPHOLIN-4-YL]-8-(TRIFLUOROMETHYL)-6,7,8,9A-TETRAHYDRO-3H-PYRIMIDO[1,2-A]PYRIMIDIN-4-ONE'>1TT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1TT:(8S)-9-[(5-CHLORANYLPYRIDIN-3-YL)METHYL]-2-[(3R)-3-METHYLMORPHOLIN-4-YL]-8-(TRIFLUOROMETHYL)-6,7,8,9A-TETRAHYDRO-3H-PYRIMIDO[1,2-A]PYRIMIDIN-4-ONE'>1TT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PIK3C3,VPS34 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=4oys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oys OCA], [https://pdbe.org/4oys PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oys RCSB], [https://www.ebi.ac.uk/pdbsum/4oys PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oys ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137] </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=4oys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oys OCA], [http://pdbe.org/4oys PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4oys RCSB], [http://www.ebi.ac.uk/pdbsum/4oys PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4oys ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PK3C3_HUMAN PK3C3_HUMAN]] Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate which plays a key role in initiation and maturation of autophagosomes. Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for the abcission step in cytokinesis. Required for transport from early to late endosomes.<ref>PMID:7628435</ref> <ref>PMID:14617358</ref> <ref>PMID:20208530</ref>
+[https://www.uniprot.org/uniprot/PK3C3_HUMAN PK3C3_HUMAN] Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate which plays a key role in initiation and maturation of autophagosomes. Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for the abcission step in cytokinesis. Required for transport from early to late endosomes.<ref>PMID:7628435</ref> <ref>PMID:14617358</ref> <ref>PMID:20208530</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 20: @@
 ==See Also==
-*[[Phosphoinositide 3-Kinases|Phosphoinositide 3-Kinases]]
+*[[Phosphoinositide 3-kinase 3D structures|Phosphoinositide 3-kinase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Phosphatidylinositol 3-kinase]]
+[[Category: Large Structures]]
-[[Category: Marquette, J p]]
+[[Category: Marquette Jp]]
-[[Category: Mathieu, M]]
+[[Category: Mathieu M]]
-[[Category: Lipid kinase]]

4oys

From Proteopedia

Revision as of 12:32, 1 February 2023

CRYSTAL STRUCTURE OF VPS34 IN COMPLEX WITH SAR405.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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