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| | <StructureSection load='6qfc' size='340' side='right'caption='[[6qfc]], [[Resolution|resolution]] 1.96Å' scene=''> | | <StructureSection load='6qfc' size='340' side='right'caption='[[6qfc]], [[Resolution|resolution]] 1.96Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6qfc]] is a 2 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=6QFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QFC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6qfc]] is a 2 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=6QFC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QFC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.96Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6fs0|6fs0]], [[6qb3|6qb3]], [[6qb4|6qb4]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCL1, BCL2L3 ([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=6qfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qfc OCA], [https://pdbe.org/6qfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qfc RCSB], [https://www.ebi.ac.uk/pdbsum/6qfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qfc ProSAT]</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=6qfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qfc OCA], [http://pdbe.org/6qfc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qfc RCSB], [http://www.ebi.ac.uk/pdbsum/6qfc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qfc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| | + | *[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] |
| | *[[Kallikrein 3D structures|Kallikrein 3D structures]] | | *[[Kallikrein 3D structures|Kallikrein 3D structures]] |
| | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Luptak, J]] | + | [[Category: Luptak J]] |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Mcl1]]
| + | |
| - | [[Category: Scfv]]
| + | |
| Structural highlights
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
Apoptosis is a crucial process by which multicellular organisms control tissue growth, removal and inflammation. Disruption of the normal apoptotic function is often observed in cancer, where cell death is avoided by the overexpression of anti-apoptotic proteins of the Bcl-2 (B-cell lymphoma 2) family, including Mcl-1 (myeloid cell leukaemia 1). This makes Mcl-1 a potential target for drug therapy, through which normal apoptosis may be restored by inhibiting the protective function of Mcl-1. Here, the discovery and biophysical properties of an anti-Mcl-1 antibody fragment are described and the utility of both the scFv and Fab are demonstrated in generating an Mcl-1 crystal system amenable to iterative structure-guided drug design.
Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1.,Luptak J, Bista M, Fisher D, Flavell L, Gao N, Wickson K, Kazmirski SL, Howard T, Rawlins PB, Hargreaves D Acta Crystallogr D Struct Biol. 2019 Nov 1;75(Pt 11):1003-1014. doi:, 10.1107/S2059798319014116. Epub 2019 Oct 31. PMID:31692474[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Luptak J, Bista M, Fisher D, Flavell L, Gao N, Wickson K, Kazmirski SL, Howard T, Rawlins PB, Hargreaves D. Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1. Acta Crystallogr D Struct Biol. 2019 Nov 1;75(Pt 11):1003-1014. doi:, 10.1107/S2059798319014116. Epub 2019 Oct 31. PMID:31692474 doi:http://dx.doi.org/10.1107/S2059798319014116
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