2o36

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{{Seed}}
 
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[[Image:2o36.png|left|200px]]
 
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==Crystal structure of engineered thimet oligopeptidase with neurolysin specificity in neurotensin cleavage site==
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The line below this paragraph, containing "STRUCTURE_2o36", creates the "Structure Box" on the page.
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<StructureSection load='2o36' size='340' side='right'caption='[[2o36]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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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'>[[2o36]] 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=2O36 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2O36 FirstGlance]. <br>
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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]] 1.95&#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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{{STRUCTURE_2o36| PDB=2o36 | 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=2o36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o36 OCA], [https://pdbe.org/2o36 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o36 RCSB], [https://www.ebi.ac.uk/pdbsum/2o36 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o36 ProSAT]</span></td></tr>
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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/o3/2o36_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=2o36 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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Thimet oligopeptidase (EC 3.4.24.15) and neurolysin (EC 3.4.24.16) are closely related zinc-dependent metallopeptidases that metabolize small bioactive peptides. They cleave many substrates at the same sites, but they recognize different positions on others, including neurotensin, a 13-residue peptide involved in modulation of dopaminergic circuits, pain perception, and thermoregulation. On the basis of crystal structures and previous mapping studies, four sites (Glu-469/Arg-470, Met-490/Arg-491, His-495/Asn-496, and Arg-498/Thr-499; thimet oligopeptidase residues listed first) in their substrate-binding channels appear positioned to account for differences in specificity. Thimet oligopeptidase mutated so that neurolysin residues are at all four positions cleaves neurotensin at the neurolysin site, and the reverse mutations in neurolysin switch hydrolysis to the thimet oligopeptidase site. Using a series of constructs mutated at just three of the sites, it was determined that mutations at only two (Glu-469/Arg-470 and Arg-498/Thr-499) are required to swap specificity, a result that was confirmed by testing the two-mutant constructs. If only either one of the two sites is mutated in thimet oligopeptidase, then the enzyme cleaves almost equally at the two hydrolysis positions. Crystal structures of both two-mutant constructs show that the mutations do not perturb local structure, but side chain conformations at the Arg-498/Thr-499 position differ from those of the mimicked enzyme. A model for differential recognition of neurotensin based on differences in surface charge distribution in the substrate binding sites is proposed. The model is supported by the finding that reducing the positive charge on the peptide results in cleavage at both hydrolysis sites.
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===Crystal structure of engineered thimet oligopeptidase with neurolysin specificity in neurotensin cleavage site===
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Swapping the substrate specificities of the neuropeptidases neurolysin and thimet oligopeptidase.,Lim EJ, Sampath S, Coll-Rodriguez J, Schmidt J, Ray K, Rodgers DW J Biol Chem. 2007 Mar 30;282(13):9722-32. Epub 2007 Jan 24. PMID:17251185<ref>PMID:17251185</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 class="pdbe-citations 2o36" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 17251185 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_17251185}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2O36 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O36 OCA].
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==Reference==
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<ref group="xtra">PMID:17251185</ref><ref group="xtra">PMID:14998993</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Thimet oligopeptidase]]
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[[Category: Large Structures]]
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[[Category: Lim, E J.]]
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[[Category: Lim EJ]]
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[[Category: Rodgers, D W.]]
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[[Category: Rodgers DW]]
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[[Category: Substrate-binding channel]]
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[[Category: Thermolysin-like domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 14:17:04 2009''
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Current revision

Crystal structure of engineered thimet oligopeptidase with neurolysin specificity in neurotensin cleavage site

PDB ID 2o36

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