4ce2

From Proteopedia

(Difference between revisions)

Revision as of 15:33, 25 December 2014

Hsp90 N-terminal domain bound to macrolactam analogues of radicicol.

Structural highlights

4ce2 is a 1 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4ce1, 4ce3
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[HSP82_YEAST] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. The nucleotide-free form of the dimer is found in an open conformation in which the N-termini are not dimerized and the complex is ready for client protein binding. Binding of ATP induces large conformational changes, resulting in the formation of a ring-like closed structure in which the N-terminal domains associate intramolecularly with the middle domain and also dimerize with each other, stimulating their intrinsic ATPase activity and acting as a clamp on the substrate. Finally, ATP hydrolysis results in the release of the substrate. 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. Required for growth at high temperatures.^[1]

Publication Abstract from PubMed

A series of macrolactam analogues of the naturally occurring resorcylic acid lactone radicicol have been synthesised from methyl orsellinate in 7 steps, involving chlorination, protection of the two phenolic groups, and hydrolysis to the benzoic acid. Formation of the dianion and quenching with a Weinreb amide results in acylation of the toluene methyl group that is followed by amide formation and ring closing metathesis to form the macrocyclic lactam. Final deprotection of the phenolic groups gives the desired macrolactams whose binding to the N-terminal domain of yeast Hsp90 was studied by isothermal titration calorimetry and protein X-ray crystallography.

Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90.,Dutton BL, Kitson RR, Parry-Morris S, Roe SM, Prodromou C, Moody CJ Org Biomol Chem. 2014 Jan 17. PMID:24435512^[2]

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

References

↑ Proisy N, Sharp SY, Boxall K, Connelly S, Roe SM, Prodromou C, Slawin AM, Pearl LH, Workman P, Moody CJ. Inhibition of Hsp90 with synthetic macrolactones: synthesis and structural and biological evaluation of ring and conformational analogs of radicicol. Chem Biol. 2006 Nov;13(11):1203-15. PMID:17114002 doi:10.1016/j.chembiol.2006.09.015
↑ Dutton BL, Kitson RR, Parry-Morris S, Roe SM, Prodromou C, Moody CJ. Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90. Org Biomol Chem. 2014 Jan 17. PMID:24435512 doi:http://dx.doi.org/10.1039/c3ob42211a

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ce2"

Categories: Atcc 18824 | Parry-Morris, S | Prodromou, C | Roe, S M | Chaperone

@@ Line 7: / Line 7: @@
 <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=4ce2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ce2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ce2 RCSB], [http://www.ebi.ac.uk/pdbsum/4ce2 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/HSP82_YEAST HSP82_YEAST]] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. The nucleotide-free form of the dimer is found in an open conformation in which the N-termini are not dimerized and the complex is ready for client protein binding. Binding of ATP induces large conformational changes, resulting in the formation of a ring-like closed structure in which the N-terminal domains associate intramolecularly with the middle domain and also dimerize with each other, stimulating their intrinsic ATPase activity and acting as a clamp on the substrate. Finally, ATP hydrolysis results in the release of the substrate. 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. Required for growth at high temperatures.<ref>PMID:17114002</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4ce2

From Proteopedia

Revision as of 15:33, 25 December 2014

Hsp90 N-terminal domain bound to macrolactam analogues of radicicol.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox