4wgi

From Proteopedia

(Difference between revisions)

Current revision

A Single Diastereomer of a Macrolactam Core Binds Specifically to Myeloid Cell Leukemia 1 (MCL1)

Structural highlights

4wgi is a 1 chain structure with sequence from Escherichia coli O157:H7 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.85Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MALE_ECO57 Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides (By similarity).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 direct binding screen of 100 000 sp(3)-rich molecules identified a single diastereomer of a macrolactam core that binds specifically to myeloid cell leukemia 1 (MCL1). A comprehensive toolbox of biophysical methods was applied to validate the original hit and subsequent analogues and also established a binding mode competitive with NOXA BH3 peptide. X-ray crystallography of ligand bound to MCL1 reveals a remarkable ligand/protein shape complementarity that diverges from previously disclosed MCL1 inhibitor costructures.

Single Diastereomer of a Macrolactam Core Binds Specifically to Myeloid Cell Leukemia 1 (MCL1).,Fang C, D'Souza B, Thompson CF, Clifton MC, Fairman JW, Fulroth B, Leed A, McCarren P, Wang L, Wang Y, Feau C, Kaushik VK, Palmer M, Wei G, Golub TR, Hubbard BK, Serrano-Wu MH ACS Med Chem Lett. 2014 Nov 11;5(12):1308-12. doi: 10.1021/ml500388q. eCollection, 2014 Dec 11. PMID:25516789^[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
↑ Fang C, D'Souza B, Thompson CF, Clifton MC, Fairman JW, Fulroth B, Leed A, McCarren P, Wang L, Wang Y, Feau C, Kaushik VK, Palmer M, Wei G, Golub TR, Hubbard BK, Serrano-Wu MH. Single Diastereomer of a Macrolactam Core Binds Specifically to Myeloid Cell Leukemia 1 (MCL1). ACS Med Chem Lett. 2014 Nov 11;5(12):1308-12. doi: 10.1021/ml500388q. eCollection, 2014 Dec 11. PMID:25516789 doi:http://dx.doi.org/10.1021/ml500388q

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/4wgi"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4wgi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WGI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WGI FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3M6:(2S)-2-[(2S,3R)-10-{[(4-FLUOROPHENYL)SULFONYL]AMINO}-3-METHYL-2-[(METHYL{[4-(TRIFLUOROMETHYL)PHENYL]CARBAMOYL}AMINO)METHYL]-6-OXO-3,4-DIHYDRO-2H-1,5-BENZOXAZOCIN-5(6H)-YL]PROPANOIC+ACID'>3M6</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</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]] 1.85&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3M6:(2S)-2-[(2S,3R)-10-{[(4-FLUOROPHENYL)SULFONYL]AMINO}-3-METHYL-2-[(METHYL{[4-(TRIFLUOROMETHYL)PHENYL]CARBAMOYL}AMINO)METHYL]-6-OXO-3,4-DIHYDRO-2H-1,5-BENZOXAZOCIN-5(6H)-YL]PROPANOIC+ACID'>3M6</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</scene></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=4wgi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wgi OCA], [https://pdbe.org/4wgi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wgi RCSB], [https://www.ebi.ac.uk/pdbsum/4wgi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wgi ProSAT]</span></td></tr>
 </table>

4wgi

From Proteopedia

Current revision

A Single Diastereomer of a Macrolactam Core Binds Specifically to Myeloid Cell Leukemia 1 (MCL1)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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