2hu7: Difference between revisions
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==Binding of inhibitors by Acylaminoacyl peptidase== | |||
<StructureSection load='2hu7' size='340' side='right'caption='[[2hu7]], [[Resolution|resolution]] 2.01Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2hu7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aeropyrum_pernix Aeropyrum pernix]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HU7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HU7 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]] 2.01Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PHE:PHENYLALANINE'>PHE</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=2hu7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hu7 OCA], [https://pdbe.org/2hu7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hu7 RCSB], [https://www.ebi.ac.uk/pdbsum/2hu7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hu7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/APEH_AERPE APEH_AERPE] This enzyme catalyzes the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N-acetylated amino acid and a peptide with a free N-terminus. | |||
== 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/hu/2hu7_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=2hu7 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mammalian acylaminoacyl peptidase, a member of the prolyl oligopeptidase family of serine peptidases, is an exopeptidase, which removes acylated amino acid residues from the N terminus of oligopeptides. We have investigated the kinetics and inhibitor binding of the orthologous acylaminoacyl peptidase from the thermophile Aeropyrum pernix K1 (ApAAP). Complex pH-rate profiles were found with charged substrates, indicating a strong electrostatic effect in the surroundings of the active site. Unexpectedly, we have found that oligopeptides can be hydrolysed beyond the N-terminal peptide bond, demonstrating that ApAAP exhibits endopeptidase activity. It was thought that the enzyme is specific for hydrophobic amino acids, in particular phenylalanine, in accord with the non-polar S1 subsite of ApAAP. However, cleavage after an Ala residue contradicted this notion and demonstrated that P1 residues of different nature may bind to the S1 subsite depending on the remaining peptide residues. The crystal structures of the complexes formed between the enzyme and product-like inhibitors identified the oxyanion-binding site unambiguously and demonstrated that the phenylalanine ring of the P1 peptide residue assumes a position different from that established in a previous study, using 4-nitrophenylphosphate. We have found that the substrate-binding site extends beyond the S2 subsite, being capable of binding peptides with a longer N terminus. The S2 subsite displays a non-polar character, which is unique among the enzymes of this family. The S3 site was identified as a hydrophobic region that does not form hydrogen bonds with the inhibitor P3 residue. The enzyme-inhibitor complexes revealed that, upon ligand-binding, the S1 subsite undergoes significant conformational changes, demonstrating the plasticity of the specificity site. | |||
The acylaminoacyl peptidase from Aeropyrum pernix K1 thought to be an exopeptidase displays endopeptidase activity.,Kiss AL, Hornung B, Radi K, Gengeliczki Z, Sztaray B, Juhasz T, Szeltner Z, Harmat V, Polgar L J Mol Biol. 2007 Apr 27;368(2):509-20. Epub 2007 Feb 20. PMID:17350041<ref>PMID:17350041</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2hu7" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Acylaminoacyl peptidase|Acylaminoacyl peptidase]] | |||
[[ | *[[Acylaminoacyl peptidase 3D structures|Acylaminoacyl peptidase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Aeropyrum pernix]] | [[Category: Aeropyrum pernix]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Gengeliczki | [[Category: Gengeliczki Z]] | ||
[[Category: Harmat | [[Category: Harmat V]] | ||
[[Category: Hornung | [[Category: Hornung B]] | ||
[[Category: Kiss | [[Category: Kiss AL]] | ||
[[Category: Polgar | [[Category: Polgar L]] | ||
[[Category: Radi | [[Category: Radi K]] | ||
[[Category: Sztaray | [[Category: Sztaray B]] | ||
Latest revision as of 11:51, 25 October 2023
Binding of inhibitors by Acylaminoacyl peptidaseBinding of inhibitors by Acylaminoacyl peptidase
Structural highlights
FunctionAPEH_AERPE This enzyme catalyzes the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N-acetylated amino acid and a peptide with a free N-terminus. 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 PubMedMammalian acylaminoacyl peptidase, a member of the prolyl oligopeptidase family of serine peptidases, is an exopeptidase, which removes acylated amino acid residues from the N terminus of oligopeptides. We have investigated the kinetics and inhibitor binding of the orthologous acylaminoacyl peptidase from the thermophile Aeropyrum pernix K1 (ApAAP). Complex pH-rate profiles were found with charged substrates, indicating a strong electrostatic effect in the surroundings of the active site. Unexpectedly, we have found that oligopeptides can be hydrolysed beyond the N-terminal peptide bond, demonstrating that ApAAP exhibits endopeptidase activity. It was thought that the enzyme is specific for hydrophobic amino acids, in particular phenylalanine, in accord with the non-polar S1 subsite of ApAAP. However, cleavage after an Ala residue contradicted this notion and demonstrated that P1 residues of different nature may bind to the S1 subsite depending on the remaining peptide residues. The crystal structures of the complexes formed between the enzyme and product-like inhibitors identified the oxyanion-binding site unambiguously and demonstrated that the phenylalanine ring of the P1 peptide residue assumes a position different from that established in a previous study, using 4-nitrophenylphosphate. We have found that the substrate-binding site extends beyond the S2 subsite, being capable of binding peptides with a longer N terminus. The S2 subsite displays a non-polar character, which is unique among the enzymes of this family. The S3 site was identified as a hydrophobic region that does not form hydrogen bonds with the inhibitor P3 residue. The enzyme-inhibitor complexes revealed that, upon ligand-binding, the S1 subsite undergoes significant conformational changes, demonstrating the plasticity of the specificity site. The acylaminoacyl peptidase from Aeropyrum pernix K1 thought to be an exopeptidase displays endopeptidase activity.,Kiss AL, Hornung B, Radi K, Gengeliczki Z, Sztaray B, Juhasz T, Szeltner Z, Harmat V, Polgar L J Mol Biol. 2007 Apr 27;368(2):509-20. Epub 2007 Feb 20. PMID:17350041[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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