4z1f

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: '''Unreleased structure''' The entry 4z1f is ON HOLD Authors: Lee, C., Park, H.-K., Ryu, J.-H., Kang, B.H. Description: Crystal structure of human Trap1 with PU-H71 [[Category: Unrelea...)
Current revision (07:35, 10 May 2023) (edit) (undo)
 
(5 intermediate revisions not shown.)
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 4z1f is ON HOLD
+
==Crystal structure of human Trap1 with PU-H71==
 +
<StructureSection load='4z1f' size='340' side='right'caption='[[4z1f]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[4z1f]] 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=4Z1F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z1F FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H71:8-[(6-IODO-1,3-BENZODIOXOL-5-YL)THIO]-9-[3-(ISOPROPYLAMINO)PROPYL]-9H-PURIN-6-AMINE'>H71</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=4z1f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z1f OCA], [https://pdbe.org/4z1f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z1f RCSB], [https://www.ebi.ac.uk/pdbsum/4z1f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z1f ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/TRAP1_HUMAN TRAP1_HUMAN] Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, most likely through stabilization of mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA.<ref>PMID:23525905</ref> <ref>PMID:23564345</ref> <ref>PMID:23747254</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
The mitochondrial pool of Hsp90 and its mitochondrial paralogue, TRAP1, suppresses cell death and reprograms energy metabolism in cancer cells; therefore, Hsp90 and TRAP1 have been suggested as target proteins for anticancer drug development. Here, we report that the actual target protein in cancer cell mitochondria is TRAP1, and current Hsp90 inhibitors cannot effectively inactivate TRAP1 because of their insufficient accumulation in the mitochondria. To develop mitochondrial TRAP1 inhibitors, we determined the crystal structures of human TRAP1 complexed with Hsp90 inhibitors. The isopropyl amine of the Hsp90 inhibitor PU-H71 was replaced with the mitochondria-targeting moiety triphenylphosphonium to produce SMTIN-P01. SMTIN-P01 showed a different mode of action from the nontargeted PU-H71, as well as much improved cytotoxicity to cancer cells. In addition, we determined the structure of a TRAP1-adenylyl-imidodiphosphate (AMP-PNP) complex. On the basis of comparative analysis of TRAP1 structures, we propose a molecular mechanism of ATP hydrolysis that is crucial for chaperone function.
-
Authors: Lee, C., Park, H.-K., Ryu, J.-H., Kang, B.H.
+
Development of a Mitochondria-Targeted Hsp90 Inhibitor Based on the Crystal Structures of Human TRAP1.,Lee C, Park HK, Jeong H, Lim J, Lee AJ, Cheon KY, Kim CS, Thomas AP, Bae B, Kim ND, Kim SH, Suh PG, Ryu JH, Kang BH J Am Chem Soc. 2015 Apr 8;137(13):4358-67. doi: 10.1021/ja511893n. Epub 2015 Mar , 30. PMID:25785725<ref>PMID:25785725</ref>
-
Description: Crystal structure of human Trap1 with PU-H71
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
-
[[Category: Kang, B.H]]
+
<div class="pdbe-citations 4z1f" style="background-color:#fffaf0;"></div>
-
[[Category: Lee, C]]
+
 
-
[[Category: Ryu, J.-H]]
+
==See Also==
-
[[Category: Park, H.-K]]
+
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Homo sapiens]]
 +
[[Category: Large Structures]]
 +
[[Category: Kang BH]]
 +
[[Category: Lee C]]
 +
[[Category: Park HK]]
 +
[[Category: Ryu JH]]

Current revision

Crystal structure of human Trap1 with PU-H71

PDB ID 4z1f

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4z1f"
Personal tools