3eq8: Difference between revisions
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==Prolyl oligopeptidase complexed with R-Pro-(decarboxy-Pro)-Type inhibitors== | |||
<StructureSection load='3eq8' size='340' side='right'caption='[[3eq8]], [[Resolution|resolution]] 2.73Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3eq8]] 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=3EQ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EQ8 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]] 2.73Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=X98:1-{3-OXO-3-[(2S)-2-(PYRROLIDIN-1-YLCARBONYL)PYRROLIDIN-1-YL]PROPYL}-3-PHENYLQUINOXALIN-2(1H)-ONE'>X98</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=3eq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eq8 OCA], [https://pdbe.org/3eq8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3eq8 RCSB], [https://www.ebi.ac.uk/pdbsum/3eq8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3eq8 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/eq/3eq8_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=3eq8 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Three novel, N-acyl-pro-pyrrolidine-type, inhibitors of prolyl oligopeptidase (POP) with nanomolar activities were synthesized and their binding analyzed to the host enzyme in the light of X-ray diffraction and molecular modeling studies. We were interested in the alteration in the binding affinity at the S3 site as a function of the properties of the N-terminal group of the inhibitors. Our studies revealed that, for inhibitors with flat aromatic terminal groups, the optimal length of the linker chain is three C-C bonds, but this increases to four C-C bonds if there is a bulky group in the terminal position. Molecular dynamics calculations indicate that this is due to the better fit into the binding pocket. A 4-fold enhancement of the inhibitor activity upon replacement of the 4-CH2 group of the proline ring by CF2 is a consequence of a weak hydrogen bond formed between the fluorine atom and the hydroxy group of Tyr473 of the host enzyme. There is notably good agreement between the calculated and experimental free energies of binding; the average error in the IC50 values is around 1 order of magnitude. | |||
Prolyl oligopeptidase inhibition by N-acyl-pro-pyrrolidine-type molecules.,Kanai K, Aranyi P, Bocskei Z, Ferenczy G, Harmat V, Simon K, Batori S, Naray-Szabo G, Hermecz I J Med Chem. 2008 Dec 11;51(23):7514-22. PMID:19006380<ref>PMID:19006380</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3eq8" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Prolyl Endopeptidase|Prolyl Endopeptidase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
== | |||
< | |||
[[Category: | |||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
[[Category: Aranyi | [[Category: Aranyi P]] | ||
[[Category: Bocskei | [[Category: Bocskei Z]] | ||
[[Category: Ferenczy | [[Category: Ferenczy G]] | ||
[[Category: Harmat | [[Category: Harmat V]] | ||
[[Category: Hermecz | [[Category: Hermecz I]] | ||
[[Category: Kanai | [[Category: Kanai K]] | ||
[[Category: Naray-Szabo | [[Category: Naray-Szabo G]] | ||
[[Category: Simon | [[Category: Simon K]] | ||
Latest revision as of 18:22, 1 November 2023
Prolyl oligopeptidase complexed with R-Pro-(decarboxy-Pro)-Type inhibitorsProlyl oligopeptidase complexed with R-Pro-(decarboxy-Pro)-Type inhibitors
Structural highlights
FunctionPPCE_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 Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThree novel, N-acyl-pro-pyrrolidine-type, inhibitors of prolyl oligopeptidase (POP) with nanomolar activities were synthesized and their binding analyzed to the host enzyme in the light of X-ray diffraction and molecular modeling studies. We were interested in the alteration in the binding affinity at the S3 site as a function of the properties of the N-terminal group of the inhibitors. Our studies revealed that, for inhibitors with flat aromatic terminal groups, the optimal length of the linker chain is three C-C bonds, but this increases to four C-C bonds if there is a bulky group in the terminal position. Molecular dynamics calculations indicate that this is due to the better fit into the binding pocket. A 4-fold enhancement of the inhibitor activity upon replacement of the 4-CH2 group of the proline ring by CF2 is a consequence of a weak hydrogen bond formed between the fluorine atom and the hydroxy group of Tyr473 of the host enzyme. There is notably good agreement between the calculated and experimental free energies of binding; the average error in the IC50 values is around 1 order of magnitude. Prolyl oligopeptidase inhibition by N-acyl-pro-pyrrolidine-type molecules.,Kanai K, Aranyi P, Bocskei Z, Ferenczy G, Harmat V, Simon K, Batori S, Naray-Szabo G, Hermecz I J Med Chem. 2008 Dec 11;51(23):7514-22. PMID:19006380[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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