4jql

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 Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	HSP90AA1, HSP90A, HSPC1, HSPCA (HUMAN)
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]

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^[3]

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

References

↑ 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
↑ 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
↑ Jeso V, Iqbal S, Hernandez P, Cameron MD, Park H, Lograsso PV, Micalizio GC. Synthesis of benzoquinone ansamycin-inspired macrocyclic lactams from shikimic Acid. Angew Chem Int Ed Engl. 2013 Apr 26;52(18):4800-4. doi: 10.1002/anie.201301323., Epub 2013 Apr 2. PMID:23554224 doi:10.1002/anie.201301323

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OCA

[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

[3] Jeso V, Iqbal S, Hernandez P, Cameron MD, Park H, Lograsso PV, Micalizio GC. Synthesis of benzoquinone ansamycin-inspired macrocyclic lactams from shikimic Acid. Angew Chem Int Ed Engl. 2013 Apr 26;52(18):4800-4. doi: 10.1002/anie.201301323., Epub 2013 Apr 2. PMID:23554224 doi:10.1002/anie.201301323

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