5trs

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (14:22, 6 March 2024) (edit) (undo)
 
Line 3: Line 3:
<StructureSection load='5trs' size='340' side='right'caption='[[5trs]], [[Resolution|resolution]] 3.08&Aring;' scene=''>
<StructureSection load='5trs' size='340' side='right'caption='[[5trs]], [[Resolution|resolution]] 3.08&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[5trs]] is a 28 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TRS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TRS FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[5trs]] is a 28 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TRS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TRS FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7HZ:N-TERT-BUTOXY-N~2~-(5-METHYL-1,2-OXAZOLE-3-CARBONYL)-L-ASPARAGINYL-O-METHYL-N-[(NAPHTHALEN-1-YL)METHYL]-L-SERINAMIDE'>7HZ</scene></td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.083567&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5trg|5trg]], [[5trr|5trr]], [[5try|5try]], [[5ts9|5ts9]]</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7HZ:N-TERT-BUTOXY-N~2~-(5-METHYL-1,2-OXAZOLE-3-CARBONYL)-L-ASPARAGINYL-O-METHYL-N-[(NAPHTHALEN-1-YL)METHYL]-L-SERINAMIDE'>7HZ</scene></td></tr>
-
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">prcA, MRA_2124 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884]), prcB, MRA_2125 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=5trs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5trs OCA], [https://pdbe.org/5trs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5trs RCSB], [https://www.ebi.ac.uk/pdbsum/5trs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5trs ProSAT]</span></td></tr>
-
<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>
+
-
<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=5trs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5trs OCA], [http://pdbe.org/5trs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5trs RCSB], [http://www.ebi.ac.uk/pdbsum/5trs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5trs ProSAT]</span></td></tr>
+
</table>
</table>
== Function ==
== Function ==
-
[[http://www.uniprot.org/uniprot/PSA_MYCTA PSA_MYCTA]] Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. [[http://www.uniprot.org/uniprot/PSB_MYCTA PSB_MYCTA]] Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation.
+
[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>
-
<div style="background-color:#fffaf0;">
+
-
== Publication Abstract from PubMed ==
+
-
The Mycobacterium tuberculosis (Mtb) 20S proteasome is vital for the pathogen to survive under nitrosative stress in vitro and to persist in mice. To qualify for drug development, inhibitors targeting Mtb 20S must spare both the human constitutive proteasome (c-20S) and immunoproteasome (i-20S). We recently reported members of a family of noncovalently binding dipeptide proteasome inhibitors that are highly potent and selective for Mtb 20S over human c-20S and i-20S. To understand the structural basis of their potency and selectivity, we have studied the structure-activity relationship of six derivatives and solved their cocrystal structures with Mtb 20S. The dipeptide inhibitors form an antiparallel beta-strand with the active site beta-strands. Selectivity is conferred by several features of Mtb 20S relative to its mouse counterparts, including a larger S1 pocket, additional hydrogen bonds in the S3 pocket, and hydrophobic interactions in the S4 pocket. Serine-20 and glutamine-22 of Mtb 20S interact with the dipeptides and confer Mtb-specific inhibition over c-20S and i-20S. The Mtb 20S and mammalian i-20S have a serine-27 that interacts strongly with the dipeptides, potentially explaining the higher inhibitory activity of the dipeptides toward i-20S over c-20S. This detailed structural knowledge will aid in optimizing the dipeptides as anti-tuberculosis drugs.
+
-
 
+
-
Structural Basis for the Species-Selective Binding of N,C-Capped Dipeptides to the Mycobacterium tuberculosis Proteasome.,Hsu HC, Singh PK, Fan H, Wang R, Sukenick G, Nathan C, Lin G, Li H Biochemistry. 2017 Jan 10;56(1):324-333. doi: 10.1021/acs.biochem.6b01107. Epub, 2016 Dec 27. PMID:27976853<ref>PMID:27976853</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 5trs" style="background-color:#fffaf0;"></div>
+
==See Also==
==See Also==
Line 29: Line 18:
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Proteasome endopeptidase complex]]
 
-
[[Category: Fan, H]]
 
-
[[Category: Hsu, H C]]
 
-
[[Category: Li, H]]
 
-
[[Category: Lin, G]]
 
-
[[Category: Nathan, C]]
 
-
[[Category: Singh, P K]]
 
-
[[Category: Sukenick, G]]
 
-
[[Category: Wang, R]]
 
-
[[Category: C-capped dipeptide]]
 
-
[[Category: Hydrolase-hydrolase inhibitor complex]]
 
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
-
[[Category: Proteasome]]
+
[[Category: Fan H]]
 +
[[Category: Hsu H-C]]
 +
[[Category: Li H]]
 +
[[Category: Lin G]]
 +
[[Category: Nathan C]]
 +
[[Category: Singh PK]]
 +
[[Category: Sukenick G]]
 +
[[Category: Wang R]]

Current revision

Structure of Mycobacterium tuberculosis proteasome in complex with N,C-capped dipeptide PKS2144

PDB ID 5trs

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools