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1s4b

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(New page: 200px<br /> <applet load="1s4b" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s4b, resolution 2.00&Aring;" /> '''Crystal structure o...)
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[[Image:1s4b.gif|left|200px]]<br />
 
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<applet load="1s4b" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1s4b, resolution 2.00&Aring;" />
 
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'''Crystal structure of human thimet oligopeptidase.'''<br />
 
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==Overview==
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==Crystal structure of human thimet oligopeptidase.==
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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.
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<StructureSection load='1s4b' size='340' side='right'caption='[[1s4b]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<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>
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1S4B 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 ZN 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S4B OCA].
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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&#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=ZN:ZINC+ION'>ZN</scene></td></tr>
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==Reference==
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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=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>
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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]
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</table>
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== Function ==
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[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.
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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/s4/1s4b_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/main_output.php?pdb_ID=1s4b ConSurf].
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<div style="clear:both"></div>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Thimet oligopeptidase]]
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[[Category: Coll-Rodriguez J]]
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[[Category: Coll-Rodriguez, J.]]
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[[Category: Hines CS]]
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[[Category: Hines, C.S.]]
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[[Category: Ray K]]
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[[Category: Ray, K.]]
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[[Category: Rodgers DW]]
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[[Category: Rodgers, D.W.]]
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[[Category: ZN]]
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[[Category: zinc metallopeptidase domain]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:10:23 2007''
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Current revision

Crystal structure of human thimet oligopeptidase.

PDB ID 1s4b

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