5mrv: Difference between revisions

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'''Unreleased structure'''


The entry 5mrv is ON HOLD
==Crystal structure of human carboxypeptidase O in complex with NvCI==
<StructureSection load='5mrv' size='340' side='right'caption='[[5mrv]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mrv]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Nerita_versicolor Nerita versicolor]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MRV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MRV 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]] 1.854&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5mrv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mrv OCA], [https://pdbe.org/5mrv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mrv RCSB], [https://www.ebi.ac.uk/pdbsum/5mrv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mrv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CBPO_HUMAN CBPO_HUMAN] Carboxypeptidase which preferentially cleaves C-terminal acidic residues from peptides and proteins. Can also cleave C-terminal hydrophobic amino acids, with a preference for small residues over large residues.<ref>PMID:21921028</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human metallocarboxypeptidase O (hCPO) is a recently discovered digestive enzyme localized to the apical membrane of intestinal epithelial cells. Unlike pancreatic metallocarboxypeptidases, hCPO is glycosylated and produced as an active enzyme with distinctive substrate specificity toward C-terminal (C-t) acidic residues. Here we present the crystal structure of hCPO at 1.85-A resolution, both alone and in complex with a carboxypeptidase inhibitor (NvCI) from the marine snail Nerita versicolor The structure provides detailed information regarding determinants of enzyme specificity, in particular Arg275, placed at the bottom of the substrate-binding pocket. This residue, located at "canonical" position 255, where it is Ile in human pancreatic carboxypeptidases A1 (hCPA1) and A2 (hCPA2) and Asp in B (hCPB), plays a dominant role in determining the preference of hCPO for acidic C-t residues. Site-directed mutagenesis to Asp and Ala changes the specificity to C-t basic and hydrophobic residues, respectively. The single-site mutants thus faithfully mimic the enzymatic properties of CPB and CPA, respectively. hCPO also shows a preference for Glu over Asp, probably as a consequence of a tighter fitting of the Glu side chain in its S1' substrate-binding pocket. This unique preference of hCPO, together with hCPA1, hCPA2, and hCPB, completes the array of C-t cleavages enabling the digestion of the dietary proteins within the intestine. Finally, in addition to activity toward small synthetic substrates and peptides, hCPO can also trim C-t extensions of proteins, such as epidermal growth factor, suggesting a role in the maturation and degradation of growth factors and bioactive peptides.


Authors: Garcia-Pardo, J., Garcia-Guerrero, M.C., Fernandez-Alvarez, R., Lyons, P., Aviles, F.X., Lorenzo, J., Reverter, D.
Crystal structure and mechanism of human carboxypeptidase O: Insights into its specific activity for acidic residues.,Garcia-Guerrero MC, Garcia-Pardo J, Berenguer E, Fernandez-Alvarez R, Barfi GB, Lyons PJ, Aviles FX, Huber R, Lorenzo J, Reverter D Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):E3932-E3939. doi:, 10.1073/pnas.1803685115. Epub 2018 Apr 10. PMID:29636417<ref>PMID:29636417</ref>


Description: Crystal structure of human carboxypeptidase O in complex with NvCI
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Reverter, D]]
<div class="pdbe-citations 5mrv" style="background-color:#fffaf0;"></div>
[[Category: Garcia-Pardo, J]]
 
[[Category: Lyons, P]]
==See Also==
[[Category: Lorenzo, J]]
*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
[[Category: Aviles, F.X]]
== References ==
[[Category: Garcia-Guerrero, M.C]]
<references/>
[[Category: Fernandez-Alvarez, R]]
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Nerita versicolor]]
[[Category: Aviles FX]]
[[Category: Fernandez-Alvarez R]]
[[Category: Garcia-Guerrero MC]]
[[Category: Garcia-Pardo J]]
[[Category: Lorenzo J]]
[[Category: Lyons P]]
[[Category: Reverter D]]
Retrieved from "https://proteopedia.org/5mrv"