1s4b: Difference between revisions

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-[[Image:1s4b.gif|left|200px]]<br /><applet load="1s4b" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="1s4b, resolution 2.00&Aring;" />
-'''Crystal structure of human thimet oligopeptidase.'''<br />
-==Overview==
+==Crystal structure of human thimet oligopeptidase.==
-Thimet oligopeptidase (TOP) is a zinc metallopeptidase that metabolizes a number of bioactive peptides and degrades peptides released by the proteasome, limiting antigenic presentation by MHC class I molecules. We present the crystal structure of human TOP at 2.0-A resolution. The active site is located at the base of a deep channel that runs the length of the elongated molecule, an overall fold first seen in the closely related metallopeptidase neurolysin. Comparison of the two related structures indicates hinge-like flexibility and identifies elements near one end of the channel that adopt different conformations. Relatively few of the sequence differences between TOP and neurolysin map to the proposed substrate-binding site, and four of these variable residues may account for differences in substrate specificity. In addition, a loop segment (residues 599-611) in TOP differs in conformation and degree of order from the corresponding neurolysin loop, suggesting it may also play a role in activity differences. Cysteines thought to mediate covalent oligomerization of rat TOP, which can inactivate the enzyme, are found to be surface-accessible in the human enzyme, and additional cysteines (residues 321,350, and 644) may also mediate multimerization in the human homolog. Disorder in the N terminus of TOP indicates it may be involved in subcellular localization, but a potential nuclear import element is found to be part of a helix and, therefore, unlikely to be involved in transport. A large acidic patch on the surface could potentially mediate a protein-protein interaction, possibly through formation of a covalent linkage.
+<StructureSection load='1s4b' size='340' side='right'caption='[[1s4b]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
-==About this Structure==
+<table><tr><td colspan='2'>[[1s4b]] 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=1S4B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S4B FirstGlance]. <br>
-S4B is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Thimet_oligopeptidase Thimet oligopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.15 3.4.24.15] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S4B 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=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=1s4b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s4b OCA], [https://pdbe.org/1s4b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s4b RCSB], [https://www.ebi.ac.uk/pdbsum/1s4b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s4b ProSAT]</span></td></tr>
-Crystal structure of human thimet oligopeptidase provides insight into substrate recognition, regulation, and localization., Ray K, Hines CS, Coll-Rodriguez J, Rodgers DW, J Biol Chem. 2004 May 7;279(19):20480-9. Epub 2004 Mar 3. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14998993 14998993]
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/THOP1_HUMAN THOP1_HUMAN] Involved in the metabolism of neuropeptides under 20 amino acid residues long. Involved in cytoplasmic peptide degradation. Able to degrade the beta-amyloid precursor protein and generate amyloidogenic fragments.
+== 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/s4/1s4b_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=1s4b ConSurf].
+<div style="clear:both"></div>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Thimet oligopeptidase]]
+[[Category: Coll-Rodriguez J]]
-[[Category: Coll-Rodriguez, J.]]
+[[Category: Hines CS]]
-[[Category: Hines, C S.]]
+[[Category: Ray K]]
-[[Category: Ray, K.]]
+[[Category: Rodgers DW]]
-[[Category: Rodgers, D W.]]
-[[Category: ZN]]
-[[Category: zinc metallopeptidase domain]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:57:45 2008''