2mhs

From Proteopedia

(Difference between revisions)

Current revision

NMR Structure of human Mcl-1

Structural highlights

2mhs is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MCL1_HUMAN 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. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.^[1]

Publication Abstract from PubMed

A high-quality NMR solution structure is presented for protein hMcl-1(171-327) which comprises residues 171-327 of the human anti-apoptotic protein Mcl-1 (hMcl-1). Since this construct contains the three Bcl-2 homology (BH) sequence motifs which participate in forming a binding site for inhibitors of hMcl-1, it is deemed to be crucial for structure-based design of novel anti-cancer drugs blocking the Mcl1 related anti-apoptotic pathway. While the coordinates of an NMR solution structure for a corresponding construct of the mouse homologue (mMcl-1) are publicly available, our structure is the first atomic resolution structure reported for the 'apo form' of the human protein. Comparison of the two structures reveals that hMcl-1(171-327) exhibits a somewhat wider ligand/inhibitor binding groove as well as a different charge distribution within the BH3 binding groove. These findings strongly suggest that the availability of the human structure is of critical importance to support future design of cancer drugs.

High-quality NMR structure of human anti-apoptotic protein domain mcl-1(171-327) for cancer drug design.,Liu G, Poppe L, Aoki K, Yamane H, Lewis J, Szyperski T PLoS One. 2014 May 2;9(5):e96521. doi: 10.1371/journal.pone.0096521. eCollection , 2014. PMID:24789074^[2]

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

References

↑ Bingle CD, Craig RW, Swales BM, Singleton V, Zhou P, Whyte MK. Exon skipping in Mcl-1 results in a bcl-2 homology domain 3 only gene product that promotes cell death. J Biol Chem. 2000 Jul 21;275(29):22136-46. PMID:10766760 doi:10.1074/jbc.M909572199
↑ Liu G, Poppe L, Aoki K, Yamane H, Lewis J, Szyperski T. High-quality NMR structure of human anti-apoptotic protein domain mcl-1(171-327) for cancer drug design. PLoS One. 2014 May 2;9(5):e96521. doi: 10.1371/journal.pone.0096521. eCollection , 2014. PMID:24789074 doi:http://dx.doi.org/10.1371/journal.pone.0096521

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/2mhs"

@@ Line 1: / Line 1: @@
 ==NMR Structure of human Mcl-1==
-<StructureSection load='2mhs' size='340' side='right'caption='[[2mhs]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2mhs' size='340' side='right'caption='[[2mhs]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2mhs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MHS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MHS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2mhs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MHS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MHS FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCL1, BCL2L3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2mhs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mhs OCA], [https://pdbe.org/2mhs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mhs RCSB], [https://www.ebi.ac.uk/pdbsum/2mhs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mhs ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/MCL1_HUMAN MCL1_HUMAN]] 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. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.<ref>PMID:10766760</ref>
+[https://www.uniprot.org/uniprot/MCL1_HUMAN MCL1_HUMAN] 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. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.<ref>PMID:10766760</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Aoki, K]]
+[[Category: Aoki K]]
-[[Category: Lewis, J]]
+[[Category: Lewis J]]
-[[Category: Liu, G]]
+[[Category: Liu G]]
-[[Category: Poppe, L]]
+[[Category: Poppe L]]
-[[Category: Szyperski, T]]
+[[Category: Szyperski T]]
-[[Category: Yamane, H]]
+[[Category: Yamane H]]
-[[Category: Apoptosis]]
-[[Category: Bcl-2 family]]
-[[Category: Bh domain]]
-[[Category: Cancer drug]]
-[[Category: Gft nmr]]
-[[Category: Mcl-1]]

2mhs

From Proteopedia

Current revision

NMR Structure of human Mcl-1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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