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==Synthesis of Benzoquinone-Ansamycin-Inspired Macrocyclic Lactams from Shikimic Acid==
==Synthesis of Benzoquinone-Ansamycin-Inspired Macrocyclic Lactams from Shikimic Acid==
<StructureSection load='4jql' size='340' side='right' caption='[[4jql]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
<StructureSection load='4jql' size='340' side='right'caption='[[4jql]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4jql]] is a 1 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=4JQL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JQL FirstGlance]. <br>
<table><tr><td colspan='2'>[[4jql]] is a 1 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=4JQL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JQL FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VJ6:VALERJESOMYCIN'>VJ6</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]] 1.72&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1, HSP90A, HSPC1, HSPCA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VJ6:VALERJESOMYCIN'>VJ6</scene></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=4jql FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jql OCA], [http://pdbe.org/4jql PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jql RCSB], [http://www.ebi.ac.uk/pdbsum/4jql PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jql ProSAT]</span></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=4jql FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jql OCA], [https://pdbe.org/4jql PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jql RCSB], [https://www.ebi.ac.uk/pdbsum/4jql PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jql ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/HS90A_HUMAN HS90A_HUMAN]] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref> 
[https://www.uniprot.org/uniprot/HS90A_HUMAN HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
One is not like the other: The title approach proceeds by stepwise coupling of three relatively simple substrates. Three natural product-inspired agents are described, one of which has natural product-like toxicity for HeLa and MCF7 cells. It is isoform-selective, thus targeting Hsp90alpha/beta over Grp94, and adopts a conformation similar to that of geldanamycin when complexed with Hsp90.
 
Synthesis of benzoquinone ansamycin-inspired macrocyclic lactams from shikimic Acid.,Jeso V, Iqbal S, Hernandez P, Cameron MD, Park H, Lograsso PV, Micalizio GC Angew Chem Int Ed Engl. 2013 Apr 26;52(18):4800-4. doi: 10.1002/anie.201301323., Epub 2013 Apr 2. PMID:23554224<ref>PMID:23554224</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4jql" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Heat Shock Proteins|Heat Shock Proteins]]
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Cameron, M D]]
[[Category: Large Structures]]
[[Category: Hernandez, P]]
[[Category: Cameron MD]]
[[Category: Iqbal, S]]
[[Category: Hernandez P]]
[[Category: Jeso, V]]
[[Category: Iqbal S]]
[[Category: Lograsso, P V]]
[[Category: Jeso V]]
[[Category: Micalizio, G C]]
[[Category: Lograsso PV]]
[[Category: Park, H]]
[[Category: Micalizio GC]]
[[Category: Chaperone]]
[[Category: Park H]]
[[Category: Chaperone-inhibitor complex]]
[[Category: Cytosole]]
[[Category: Geldanamycin]]
[[Category: Hsp90]]
[[Category: Inhibitor design]]
[[Category: Nucleotide binding domain]]

Latest revision as of 15:06, 1 March 2024

Synthesis of Benzoquinone-Ansamycin-Inspired Macrocyclic Lactams from Shikimic AcidSynthesis of Benzoquinone-Ansamycin-Inspired Macrocyclic Lactams from Shikimic Acid

Structural highlights

4jql is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.72Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HS90A_HUMAN Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.[1] [2]

See Also

References

  1. ↑ Martinez-Ruiz A, Villanueva L, Gonzalez de Orduna C, Lopez-Ferrer D, Higueras MA, Tarin C, Rodriguez-Crespo I, Vazquez J, Lamas S. S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8525-30. Epub 2005 Jun 3. PMID:15937123 doi:10.1073/pnas.0407294102
  2. ↑ Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE. Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem. 2001 May 11;276(19):15571-4. Epub 2001 Mar 23. PMID:11274138 doi:10.1074/jbc.C100055200

4jql, resolution 1.72Å

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