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[[Image:1o6f.jpg|left|200px]]
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{{STRUCTURE_1o6f|  PDB=1o6f  |  SCENE=  }}
'''PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, D641A MUTANT WITH BOUND PEPTIDE LIGAND SUC-GLY-PRO'''


==PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, D641A MUTANT WITH BOUND PEPTIDE LIGAND SUC-GLY-PRO==
<StructureSection load='1o6f' size='340' side='right'caption='[[1o6f]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1o6f]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1O6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1O6F FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PRO:PROLINE'>PRO</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene></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=1o6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o6f OCA], [https://pdbe.org/1o6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1o6f RCSB], [https://www.ebi.ac.uk/pdbsum/1o6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1o6f ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PPCE_PIG PPCE_PIG] Cleaves peptide bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 amino acids long.
== 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/o6/1o6f_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=1o6f ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Prolyl oligopeptidase, a serine peptidase unrelated to trypsin and subtilisin, is implicated in memory disorders and is an important target of drug design. The catalytic competence of the Asp(641) residue of the catalytic triad (Ser(554), Asp(641), His(680)) was studied using the D641N and D641A variants of the enzyme. Both variants displayed 3 orders of magnitude reduction in k(cat)/K(m) for benzyloxycarbonyl-Gly-Pro-2-naphthylamide. Using an octapeptide substrate, the decrease was 6 orders of magnitude, whereas with Z-Gly-Pro-4-nitrophenyl ester there was virtually no change in k(cat)/K(m). This indicates that the contribution of Asp(641) is very much dependent on the substrate-leaving group, which was not the case for the classic serine peptidase, trypsin. The rate constant for benzyloxycarbonyl-Gly-Pro-thiobenzylester conformed to this series as demonstrated by a method designed for monitoring the hydrolysis of thiolesters in the presence of thiol groups. Alkylation of His(680) with Z-Gly-Pro-CH(2)Cl was concluded with similar rate constants for wild-type and D641A variant. However, kinetic measurements with Z-Gly-Pro-OH, a product-like inhibitor, indicated that the His(680) is not accessible in the enzyme variants. Crystal structure determination of these mutants revealed subtle perturbations related to the catalytic activity. Many of these observations show differences in the catalysis between trypsin and prolyl oligopeptidase.


==Overview==
Substrate-dependent competency of the catalytic triad of prolyl oligopeptidase.,Szeltner Z, Rea D, Juhasz T, Renner V, Mucsi Z, Orosz G, Fulop V, Polgar L J Biol Chem. 2002 Nov 22;277(47):44597-605. Epub 2002 Sep 11. PMID:12228249<ref>PMID:12228249</ref>
Prolyl oligopeptidase, a serine peptidase unrelated to trypsin and subtilisin, is implicated in memory disorders and is an important target of drug design. The catalytic competence of the Asp(641) residue of the catalytic triad (Ser(554), Asp(641), His(680)) was studied using the D641N and D641A variants of the enzyme. Both variants displayed 3 orders of magnitude reduction in k(cat)/K(m) for benzyloxycarbonyl-Gly-Pro-2-naphthylamide. Using an octapeptide substrate, the decrease was 6 orders of magnitude, whereas with Z-Gly-Pro-4-nitrophenyl ester there was virtually no change in k(cat)/K(m). This indicates that the contribution of Asp(641) is very much dependent on the substrate-leaving group, which was not the case for the classic serine peptidase, trypsin. The rate constant for benzyloxycarbonyl-Gly-Pro-thiobenzylester conformed to this series as demonstrated by a method designed for monitoring the hydrolysis of thiolesters in the presence of thiol groups. Alkylation of His(680) with Z-Gly-Pro-CH(2)Cl was concluded with similar rate constants for wild-type and D641A variant. However, kinetic measurements with Z-Gly-Pro-OH, a product-like inhibitor, indicated that the His(680) is not accessible in the enzyme variants. Crystal structure determination of these mutants revealed subtle perturbations related to the catalytic activity. Many of these observations show differences in the catalysis between trypsin and prolyl oligopeptidase.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1O6F is a [[Single protein]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1O6F OCA].
</div>
<div class="pdbe-citations 1o6f" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Substrate-dependent competency of the catalytic triad of prolyl oligopeptidase., Szeltner Z, Rea D, Juhasz T, Renner V, Mucsi Z, Orosz G, Fulop V, Polgar L, J Biol Chem. 2002 Nov 22;277(47):44597-605. Epub 2002 Sep 11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12228249 12228249]
*[[Prolyl Endopeptidase|Prolyl Endopeptidase]]
[[Category: Prolyl oligopeptidase]]
== References ==
[[Category: Single protein]]
<references/>
[[Category: Fulop, V.]]
__TOC__
[[Category: Rea, D.]]
</StructureSection>
[[Category: Alpha/ beta-hydrolase]]
[[Category: Large Structures]]
[[Category: Amnesia]]
[[Category: Sus scrofa]]
[[Category: Beta-propeller]]
[[Category: Fulop V]]
[[Category: Hydrolase]]
[[Category: Rea D]]
[[Category: Prolyl oligopeptidase]]
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Retrieved from "https://proteopedia.org/1o6f"