1c3r: Difference between revisions

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New page: left|200px<br /><applet load="1c3r" size="450" color="white" frame="true" align="right" spinBox="true" caption="1c3r, resolution 2.0Å" /> '''CRYSTAL STRUCTURE OF ...
 
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[[Image:1c3r.gif|left|200px]]<br /><applet load="1c3r" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1c3r, resolution 2.0&Aring;" />
'''CRYSTAL STRUCTURE OF AN HDAC HOMOLOG COMPLEXED WITH TRICHOSTATIN A'''<br />


==Overview==
==CRYSTAL STRUCTURE OF AN HDAC HOMOLOG COMPLEXED WITH TRICHOSTATIN A==
Histone deacetylases (HDACs) mediate changes in nucleosome conformation, and are important in the regulation of gene expression. HDACs are involved, in cell-cycle progression and differentiation, and their deregulation is, associated with several cancers. HDAC inhibitors, such as trichostatin A, (TSA) and suberoylanilide hydroxamic acid (SAHA), have anti-tumour, effects, as they can inhibit cell growth, induce terminal differentiation, and prevent the formation of tumours in mice models, and they are, effective in the treatment of promyelocytic leukemia. Here we describe the, structure of the histone deacetylase catalytic core, as revealed by the, crystal structure of a homologue from the hyperthermophilic bacterium, Aquifex aeolicus, that shares 35.2% identity with human HDAC1 over 375, residues, deacetylates histones in vitro and is inhibited by TSA and SAHA., The deacetylase, deacetylase-TSA and deacetylase-SAHA structures reveal an, active site consisting of a tubular pocket, a zinc-binding site and two, Asp-His charge-relay systems, and establish the mechanism of HDAC, inhibition. The residues that make up the active site and contact the, inhibitors are conserved across the HDAC family. These structures also, suggest a mechanism for the deacetylation reaction and provide a framework, for the further development of HDAC inhibitors as antitumour agents.
<StructureSection load='1c3r' size='340' side='right'caption='[[1c3r]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[1c3r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C3R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C3R FirstGlance]. <br>
1C3R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus] with ZN and TSN as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1C3R OCA].  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TSN:TRICHOSTATIN+A'>TSN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
==Reference==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1c3r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c3r OCA], [https://pdbe.org/1c3r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c3r RCSB], [https://www.ebi.ac.uk/pdbsum/1c3r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c3r ProSAT]</span></td></tr>
Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors., Finnin MS, Donigian JR, Cohen A, Richon VM, Rifkind RA, Marks PA, Breslow R, Pavletich NP, Nature. 1999 Sep 9;401(6749):188-93. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10490031 10490031]
</table>
== Function ==
[https://www.uniprot.org/uniprot/O67135_AQUAE O67135_AQUAE]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c3/1c3r_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1c3r ConSurf].
<div style="clear:both"></div>
__TOC__
</StructureSection>
[[Category: Aquifex aeolicus]]
[[Category: Aquifex aeolicus]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Donigian, J.R.]]
[[Category: Donigian JR]]
[[Category: Finnin, M.S.]]
[[Category: Finnin MS]]
[[Category: Pavletich, N.P.]]
[[Category: Pavletich NP]]
[[Category: TSN]]
[[Category: ZN]]
[[Category: alpha/beta fold]]
[[Category: charge-relay system]]
[[Category: hydroxamic acid]]
[[Category: lyase]]
[[Category: penta-coordinated zinc]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 01:02:57 2007''

Latest revision as of 09:41, 7 February 2024

CRYSTAL STRUCTURE OF AN HDAC HOMOLOG COMPLEXED WITH TRICHOSTATIN ACRYSTAL STRUCTURE OF AN HDAC HOMOLOG COMPLEXED WITH TRICHOSTATIN A

Structural highlights

1c3r is a 2 chain structure with sequence from Aquifex aeolicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

O67135_AQUAE

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

1c3r, resolution 2.00Å

Drag the structure with the mouse to rotate

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OCA
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