3mb3

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of the second bromodomain of Pleckstrin homology domain interacting protein (PHIP)

Structural highlights

3mb3 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.
Method:	X-ray diffraction, Resolution 2.25Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PHIP_HUMAN Probable regulator of the insulin and insulin-like growth factor signaling pathways. Stimulates cell proliferation through regulation of cyclin transcription and has an anti-apoptotic activity through AKT1 phosphorylation and activation. Plays a role in the regulation of cell morphology and cytoskeletal organization.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Bromodomains (BRDs) are protein interaction modules that specifically recognize epsilon-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family.

Histone recognition and large-scale structural analysis of the human bromodomain family.,Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S Cell. 2012 Mar 30;149(1):214-31. PMID:22464331^[3]

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

References

↑ Farhang-Fallah J, Randhawa VK, Nimnual A, Klip A, Bar-Sagi D, Rozakis-Adcock M. The pleckstrin homology (PH) domain-interacting protein couples the insulin receptor substrate 1 PH domain to insulin signaling pathways leading to mitogenesis and GLUT4 translocation. Mol Cell Biol. 2002 Oct;22(20):7325-36. PMID:12242307
↑ Bai SW, Herrera-Abreu MT, Rohn JL, Racine V, Tajadura V, Suryavanshi N, Bechtel S, Wiemann S, Baum B, Ridley AJ. Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration. BMC Biol. 2011 Aug 11;9:54. doi: 10.1186/1741-7007-9-54. PMID:21834987 doi:10.1186/1741-7007-9-54
↑ Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S. Histone recognition and large-scale structural analysis of the human bromodomain family. Cell. 2012 Mar 30;149(1):214-31. PMID:22464331 doi:10.1016/j.cell.2012.02.013

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3mb3"

@@ Line 1: / Line 1: @@
-[[Image:3mb3.png|left|200px]]
-<!--
+==Crystal Structure of the second bromodomain of Pleckstrin homology domain interacting protein (PHIP)==
-The line below this paragraph, containing "STRUCTURE_3mb3", creates the "Structure Box" on the page.
+<StructureSection load='3mb3' size='340' side='right'caption='[[3mb3]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3mb3]] 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=3MB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MB3 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MB3:1-METHYLPYRROLIDIN-2-ONE'>MB3</scene></td></tr>
-{{STRUCTURE_3mb3|  PDB=3mb3  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3mb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mb3 OCA], [https://pdbe.org/3mb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mb3 RCSB], [https://www.ebi.ac.uk/pdbsum/3mb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mb3 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PHIP_HUMAN PHIP_HUMAN] Probable regulator of the insulin and insulin-like growth factor signaling pathways. Stimulates cell proliferation through regulation of cyclin transcription and has an anti-apoptotic activity through AKT1 phosphorylation and activation. Plays a role in the regulation of cell morphology and cytoskeletal organization.<ref>PMID:12242307</ref> <ref>PMID:21834987</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mb/3mb3_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3mb3 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Bromodomains (BRDs) are protein interaction modules that specifically recognize epsilon-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family.
-===Crystal Structure of the second bromodomain of Pleckstrin homology domain interacting protein (PHIP)===
+Histone recognition and large-scale structural analysis of the human bromodomain family.,Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S Cell. 2012 Mar 30;149(1):214-31. PMID:22464331<ref>PMID:22464331</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3mb3" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_22464331}}, adds the Publication Abstract to the page
+*[[WD-repeat protein 3D structures|WD-repeat protein 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 22464331 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_22464331}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[3mb3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MB3 OCA].
-==Reference==
-<ref group="xtra">PMID:022464331</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Arrowsmith, C H.]]
+[[Category: Large Structures]]
-[[Category: Bountra, C.]]
+[[Category: Arrowsmith CH]]
-[[Category: Delft, F von.]]
+[[Category: Bountra C]]
-[[Category: Edwards, A M.]]
+[[Category: Edwards AM]]
-[[Category: Filippakopoulos, P.]]
+[[Category: Filippakopoulos P]]
-[[Category: Keates, T.]]
+[[Category: Keates T]]
-[[Category: Knapp, S.]]
+[[Category: Knapp S]]
-[[Category: Picaud, S.]]
+[[Category: Picaud S]]
-[[Category: SGC, Structural Genomics Consortium.]]
+[[Category: Ugochukwu E]]
-[[Category: Ugochukwu, E.]]
+[[Category: Weigelt J]]
-[[Category: Weigelt, J.]]
+[[Category: Von Delft F]]
-[[Category: Bromodomain]]
-[[Category: Dcaf14]]
-[[Category: Ddb1 and cul4 associated factor 14]]
-[[Category: Ndrp]]
-[[Category: Phip]]
-[[Category: Phosphoprotein]]
-[[Category: Pleckstrin homology domain interacting protein]]
-[[Category: Sgc]]
-[[Category: Signaling protein]]
-[[Category: Structural genomics consortium]]
-[[Category: Wd repeat]]

3mb3

From Proteopedia

Current revision

Crystal Structure of the second bromodomain of Pleckstrin homology domain interacting protein (PHIP)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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