3krd

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{{STRUCTURE_3krd| PDB=3krd | SCENE= }}
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==Crystal Structure of Mycobacterium Tuberculosis Proteasome in complex with Fellutamide B==
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===Crystal Structure of Mycobacterium Tuberculosis Proteasome in complex with Fellutamide B===
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<StructureSection load='3krd' size='340' side='right' caption='[[3krd]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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{{ABSTRACT_PUBMED_20558127}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3krd]] is a 28 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KRD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KRD FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FEB:N~2~-[(3R)-3-HYDROXYDODECANOYL]-L-ASPARAGINYL-N~1~-[(1S)-1-(HYDROXYMETHYL)-3-METHYLBUTYL]-L-GLUTAMAMIDE'>FEB</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3h6f|3h6f]], [[3h6i|3h6i]], [[3hf9|3hf9]], [[3hfa|3hfa]], [[2fhh|2fhh]], [[2fhg|2fhg]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MT2169, prcA, Rv2109c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis]), MT2170, prcB, Rv2110c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex Proteasome endopeptidase complex], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.25.1 3.4.25.1] </span></td></tr>
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<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=3krd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3krd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3krd RCSB], [http://www.ebi.ac.uk/pdbsum/3krd PDBsum]</span></td></tr>
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</table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kr/3krd_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Via high-throughput screening of a natural compound library, we have identified a lipopeptide aldehyde, fellutamide B (1), as the most potent inhibitor of the Mycobacterium tuberculosis (Mtb) proteasome tested to date. Kinetic studies reveal that 1 inhibits both Mtb and human proteasomes in a time-dependent manner under steady-state condition. Remarkably, 1 inhibits the Mtb proteasome in a single-step binding mechanism with K(i)=6.8 nM, whereas it inhibits the human proteasome beta5 active site following a two-step mechanism with K(i)=11.5 nM and K(i)(*)=0.93 nM. Co-crystallization of 1 bound to the Mtb proteasome revealed a structural basis for the tight binding of 1 to the active sites of the Mtb proteasome. The hemiacetal group of 1 in the Mtb proteasome takes the (R)-configuration, whereas in the yeast proteasome it takes the (S)-configuration, indicating that the pre-chiral CHO group of 1 binds to the active site Thr1 in a different orientation. Re-examination of the structure of the yeast proteasome in complex with 1 showed significant conformational changes at the substrate-binding cleft along the active site. These structural differences are consistent with the different kinetic mechanisms of 1 against Mtb and human proteasomes.
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==About this Structure==
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Fellutamide B is a potent inhibitor of the Mycobacterium tuberculosis proteasome.,Lin G, Li D, Chidawanyika T, Nathan C, Li H Arch Biochem Biophys. 2010 Sep 15;501(2):214-20. Epub 2010 Jun 15. PMID:20558127<ref>PMID:20558127</ref>
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[[3krd]] is a 28 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KRD OCA].
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
==See Also==
==See Also==
*[[Jmol/Visualizing large molecules|Jmol/Visualizing large molecules]]
*[[Jmol/Visualizing large molecules|Jmol/Visualizing large molecules]]
*[[Proteasome|Proteasome]]
*[[Proteasome|Proteasome]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:020558127</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Proteasome endopeptidase complex]]
[[Category: Proteasome endopeptidase complex]]
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[[Category: Li, D.]]
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[[Category: Li, D]]
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[[Category: Li, H.]]
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[[Category: Li, H]]
[[Category: Autocatalytic cleavage]]
[[Category: Autocatalytic cleavage]]
[[Category: Binding site]]
[[Category: Binding site]]
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[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Inhibition]]
[[Category: Inhibition]]
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[[Category: Mycobacterium tuberculosis]]
 
[[Category: Protease]]
[[Category: Protease]]
[[Category: Proteasome]]
[[Category: Proteasome]]

Revision as of 06:14, 18 December 2014

Crystal Structure of Mycobacterium Tuberculosis Proteasome in complex with Fellutamide B

3krd, resolution 2.50Å

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