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5vx2

From Proteopedia

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Current revision

Mcl-1 in complex with Bim-h3Pc-RT

Structural highlights

5vx2 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Gene:	MCL1, BCL2L3 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MCL1_MOUSE] Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. [B2L11_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]

Publication Abstract from PubMed

Certain BH3-only proteins transiently bind and activate Bak and Bax, initiating their oligomerization and the permeabilization of the mitochondrial outer membrane, a pivotal step in the mitochondrial pathway to apoptosis. Here we describe the first crystal structures of an activator BH3 peptide bound to Bak and illustrate their use in the design of BH3 derivatives capable of inhibiting human Bak on mitochondria. These BH3 derivatives compete for the activation site at the canonical groove, are the first engineered inhibitors of Bak activation, and support the role of key conformational transitions associated with Bak activation.

Conversion of Bim-BH3 from Activator to Inhibitor of Bak through Structure-Based Design.,Brouwer JM, Lan P, Cowan AD, Bernardini JP, Birkinshaw RW, van Delft MF, Sleebs BE, Robin AY, Wardak A, Tan IK, Reljic B, Lee EF, Fairlie WD, Call MJ, Smith BJ, Dewson G, Lessene G, Colman PM, Czabotar PE Mol Cell. 2017 Nov 16;68(4):659-672.e9. doi: 10.1016/j.molcel.2017.11.001. PMID:29149594^[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:http://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:http://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
↑ Brouwer JM, Lan P, Cowan AD, Bernardini JP, Birkinshaw RW, van Delft MF, Sleebs BE, Robin AY, Wardak A, Tan IK, Reljic B, Lee EF, Fairlie WD, Call MJ, Smith BJ, Dewson G, Lessene G, Colman PM, Czabotar PE. Conversion of Bim-BH3 from Activator to Inhibitor of Bak through Structure-Based Design. Mol Cell. 2017 Nov 16;68(4):659-672.e9. doi: 10.1016/j.molcel.2017.11.001. PMID:29149594 doi:http://dx.doi.org/10.1016/j.molcel.2017.11.001

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/5vx2"

@@ Line 1: / Line 1: @@
 ==Mcl-1 in complex with Bim-h3Pc-RT==
-<StructureSection load='5vx2' size='340' side='right' caption='[[5vx2]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
+<StructureSection load='5vx2' size='340' side='right'caption='[[5vx2]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5vx2]] is a 4 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=5VX2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VX2 FirstGlance]. <br>
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 5vx2" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
 == References ==
 <references/>
@@ Line 25: / Line 28: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Brouwer, J M]]
 [[Category: Colman, P M]]

5vx2

From Proteopedia

Current revision

Mcl-1 in complex with Bim-h3Pc-RT

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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