2vm6: Difference between revisions

Revision as of 16:06, 24 December 2014

HUMAN BCL2-A1 IN COMPLEX WITH BIM-BH3 PEPTIDE

Structural highlights

2vm6 is a 2 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:	SO4
Related:	2vm5, 2v6q
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[BIM_HUMAN] Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

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

Evasion of apoptosis is recognized as a characteristic of malignant growth. Anti-apoptotic B-cell lymphoma-2 (Bcl-2) family members have therefore emerged as potential therapeutic targets due to their critical role in proliferating cancer cells. Here, we present the crystal structure of Bfl-1, the last anti-apoptotic Bcl-2 family member to be structurally characterized, in complex with a peptide corresponding to the BH3 region of the pro-apoptotic protein Bim. The structure reveals distinct features at the peptide-binding site, likely to define the binding specificity for pro-apoptotic proteins. Superposition of the Bfl-1:Bim complex with that of Mcl-1:Bim reveals a significant local plasticity of hydrophobic interactions contributed by the Bim peptide, likely to be the basis for the multi specificity of Bim for anti-apoptotic proteins.

Completing the family portrait of the anti-apoptotic Bcl-2 proteins: crystal structure of human Bfl-1 in complex with Bim.,Herman MD, Nyman T, Welin M, Lehtio L, Flodin S, Tresaugues L, Kotenyova T, Flores A, Nordlund P FEBS Lett. 2008 Oct 29;582(25-26):3590-4. Epub 2008 Sep 21. PMID:18812174^[7]

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

References

↑ O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC. Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J. 1998 Jan 15;17(2):384-95. PMID:9430630 doi:https://dx.doi.org/10.1093/emboj/17.2.384
↑ U M, Miyashita T, Shikama Y, Tadokoro K, Yamada M. Molecular cloning and characterization of six novel isoforms of human Bim, a member of the proapoptotic Bcl-2 family. FEBS Lett. 2001 Nov 30;509(1):135-41. PMID:11734221
↑ Liu JW, Chandra D, Tang SH, Chopra D, Tang DG. Identification and characterization of Bimgamma, a novel proapoptotic BH3-only splice variant of Bim. Cancer Res. 2002 May 15;62(10):2976-81. PMID:12019181
↑ Marani M, Tenev T, Hancock D, Downward J, Lemoine NR. Identification of novel isoforms of the BH3 domain protein Bim which directly activate Bax to trigger apoptosis. Mol Cell Biol. 2002 Jun;22(11):3577-89. PMID:11997495
↑ Chen JZ, Ji CN, Gu SH, Li JX, Zhao EP, Huang Y, Huang L, Ying K, Xie Y, Mao YM. Over-expression of Bim alpha3, a novel isoform of human Bim, result in cell apoptosis. Int J Biochem Cell Biol. 2004 Aug;36(8):1554-61. PMID:15147734 doi:https://dx.doi.org/10.1016/j.biocel.2003.12.015
↑ Fukazawa H, Noguchi K, Masumi A, Murakami Y, Uehara Y. BimEL is an important determinant for induction of anoikis sensitivity by mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitors. Mol Cancer Ther. 2004 Oct;3(10):1281-8. PMID:15486195
↑ Herman MD, Nyman T, Welin M, Lehtio L, Flodin S, Tresaugues L, Kotenyova T, Flores A, Nordlund P. Completing the family portrait of the anti-apoptotic Bcl-2 proteins: crystal structure of human Bfl-1 in complex with Bim. FEBS Lett. 2008 Oct 29;582(25-26):3590-4. Epub 2008 Sep 21. PMID:18812174 doi:S0014-5793(08)00763-1

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC. Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J. 1998 Jan 15;17(2):384-95. PMID:9430630 doi:https://dx.doi.org/10.1093/emboj/17.2.384

[2] U M, Miyashita T, Shikama Y, Tadokoro K, Yamada M. Molecular cloning and characterization of six novel isoforms of human Bim, a member of the proapoptotic Bcl-2 family. FEBS Lett. 2001 Nov 30;509(1):135-41. PMID:11734221

[3] Liu JW, Chandra D, Tang SH, Chopra D, Tang DG. Identification and characterization of Bimgamma, a novel proapoptotic BH3-only splice variant of Bim. Cancer Res. 2002 May 15;62(10):2976-81. PMID:12019181

[4] Marani M, Tenev T, Hancock D, Downward J, Lemoine NR. Identification of novel isoforms of the BH3 domain protein Bim which directly activate Bax to trigger apoptosis. Mol Cell Biol. 2002 Jun;22(11):3577-89. PMID:11997495

[5] Chen JZ, Ji CN, Gu SH, Li JX, Zhao EP, Huang Y, Huang L, Ying K, Xie Y, Mao YM. Over-expression of Bim alpha3, a novel isoform of human Bim, result in cell apoptosis. Int J Biochem Cell Biol. 2004 Aug;36(8):1554-61. PMID:15147734 doi:https://dx.doi.org/10.1016/j.biocel.2003.12.015

[6] Fukazawa H, Noguchi K, Masumi A, Murakami Y, Uehara Y. BimEL is an important determinant for induction of anoikis sensitivity by mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitors. Mol Cancer Ther. 2004 Oct;3(10):1281-8. PMID:15486195

[7] Herman MD, Nyman T, Welin M, Lehtio L, Flodin S, Tresaugues L, Kotenyova T, Flores A, Nordlund P. Completing the family portrait of the anti-apoptotic Bcl-2 proteins: crystal structure of human Bfl-1 in complex with Bim. FEBS Lett. 2008 Oct 29;582(25-26):3590-4. Epub 2008 Sep 21. PMID:18812174 doi:S0014-5793(08)00763-1

[1]

[2]

[3]

[4]

[5]

[6]

[7]

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2vm6]] is a 2 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=2VM6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2VM6 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vm5|2vm5]], [[2v6q|2v6q]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vm5|2vm5]], [[2v6q|2v6q]]</td></tr>
-<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=2vm6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vm6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2vm6 RCSB], [http://www.ebi.ac.uk/pdbsum/2vm6 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=2vm6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vm6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2vm6 RCSB], [http://www.ebi.ac.uk/pdbsum/2vm6 PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/BIM_HUMAN BIM_HUMAN]] Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.<ref>PMID:9430630</ref> <ref>PMID:11734221</ref> <ref>PMID:12019181</ref> <ref>PMID:11997495</ref> <ref>PMID:15147734</ref> <ref>PMID:15486195</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 35: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Arrowsmith, C H.]]
+[[Category: Arrowsmith, C H]]
-[[Category: Berg, S Van Den.]]
+[[Category: Berg, S Van Den]]
-[[Category: Berglund, H.]]
+[[Category: Berglund, H]]
-[[Category: Busam, R D.]]
+[[Category: Busam, R D]]
-[[Category: Collins, R.]]
+[[Category: Collins, R]]
-[[Category: Dahlgren, L G.]]
+[[Category: Dahlgren, L G]]
-[[Category: Edwards, A M.]]
+[[Category: Edwards, A M]]
-[[Category: Flodin, S.]]
+[[Category: Flodin, S]]
-[[Category: Flores, A.]]
+[[Category: Flores, A]]
-[[Category: Graslund, S.]]
+[[Category: Graslund, S]]
-[[Category: Hammarstrom, M.]]
+[[Category: Hammarstrom, M]]
-[[Category: Herman, M D.]]
+[[Category: Herman, M D]]
-[[Category: Johansson, I.]]
+[[Category: Johansson, I]]
-[[Category: Kallas, A.]]
+[[Category: Kallas, A]]
-[[Category: Karlberg, T.]]
+[[Category: Karlberg, T]]
-[[Category: Kotenyova, T.]]
+[[Category: Kotenyova, T]]
-[[Category: Lehtio, L.]]
+[[Category: Lehtio, L]]
-[[Category: Moche, M.]]
+[[Category: Moche, M]]
-[[Category: Nilsson, M E.]]
+[[Category: Nilsson, M E]]
-[[Category: Nordlund, P.]]
+[[Category: Nordlund, P]]
-[[Category: Nyman, T.]]
+[[Category: Nyman, T]]
-[[Category: Persson, C.]]
+[[Category: Persson, C]]
-[[Category: Sagemark, J.]]
+[[Category: Sagemark, J]]
-[[Category: Sgc, Structural Genomics Consortium.]]
+[[Category: Structural genomic]]
-[[Category: Svensson, L.]]
+[[Category: Svensson, L]]
-[[Category: Thorsell, A G.]]
+[[Category: Thorsell, A G]]
-[[Category: Tresaugues, L.]]
+[[Category: Tresaugues, L]]
-[[Category: Weigelt, J.]]
+[[Category: Weigelt, J]]
-[[Category: Welin, M.]]
+[[Category: Welin, M]]
 [[Category: Antiapoptotic]]
 [[Category: Apoptosis]]

2vm6: Difference between revisions

Revision as of 16:06, 24 December 2014

HUMAN BCL2-A1 IN COMPLEX WITH BIM-BH3 PEPTIDE

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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