3krd

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{{Seed}}
 
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[[Image:3krd.jpg|left|200px]]
 
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==Crystal Structure of Mycobacterium Tuberculosis Proteasome in complex with Fellutamide B==
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The line below this paragraph, containing "STRUCTURE_3krd", creates the "Structure Box" on the page.
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<StructureSection load='3krd' size='340' side='right'caption='[[3krd]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3krd]] is a 42 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. 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 [https://proteopedia.org/fgij/fg.htm?mol=3KRD FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HXD:(3R)-3-HYDROXYDODECANOIC+ACID'>HXD</scene></td></tr>
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{{STRUCTURE_3krd| PDB=3krd | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3krd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3krd OCA], [https://pdbe.org/3krd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3krd RCSB], [https://www.ebi.ac.uk/pdbsum/3krd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3krd ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PSA_MYCTU PSA_MYCTU] Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. The M.tuberculosis proteasome is able to cleave oligopeptides not only after hydrophobic but also after basic, acidic and small neutral residues. Among the identified substrates of the M.tuberculosis proteasome are the pupylated FabD, PanB and Mpa proteins. One function of the proteasome is to contribute to M.tuberculosis ability to resist killing by host macrophages, since the core proteasome is essential for persistence of the pathogen during the chronic phase of infection in mice. The mechanism of protection against bactericidal chemistries of the host's immune response probably involves the degradation of proteins that are irreversibly oxidized, nitrated, or nitrosated.<ref>PMID:16468985</ref> <ref>PMID:18059281</ref>
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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/initialview03.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/main_output.php?pdb_ID=3krd 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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===Crystal Structure of Mycobacterium Tuberculosis Proteasome in complex with Fellutamide B===
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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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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3krd" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_20558127}}, adds the Publication Abstract to the page
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*[[Proteasome 3D structures|Proteasome 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 20558127 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_20558127}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Large Structures]]
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3KRD is a 28 chains structure with sequences 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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==Reference==
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<ref group="xtra">PMID:20558127</ref><references group="xtra"/>
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[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
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[[Category: Proteasome endopeptidase complex]]
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[[Category: Synthetic construct]]
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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]]
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[[Category: Autocatalytic cleavage]]
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[[Category: Binding site]]
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[[Category: Fellutamide b]]
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[[Category: Hydrolase]]
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[[Category: Inhibition]]
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[[Category: Mycobacterium tuberculosis]]
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[[Category: Protease]]
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[[Category: Proteasome]]
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[[Category: Protein subunit]]
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[[Category: Substrate specificity]]
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[[Category: Threonine protease]]
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[[Category: Virulence]]
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[[Category: Zymogen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 29 08:14:23 2010''
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Current revision

Crystal Structure of Mycobacterium Tuberculosis Proteasome in complex with Fellutamide B

PDB ID 3krd

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