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| | ==Ascaris suum carboxypeptidase inhibitor in complex with human carboxypeptidase A1== | | ==Ascaris suum carboxypeptidase inhibitor in complex with human carboxypeptidase A1== |
| - | <StructureSection load='3fju' size='340' side='right' caption='[[3fju]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='3fju' size='340' side='right'caption='[[3fju]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3fju]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ascsu Ascsu] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FJU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FJU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3fju]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ascaris_suum Ascaris suum] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FJU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FJU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2v77|2v77]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CPA1, CPA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3fju FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fju OCA], [https://pdbe.org/3fju PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fju RCSB], [https://www.ebi.ac.uk/pdbsum/3fju PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fju ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carboxypeptidase_A Carboxypeptidase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.1 3.4.17.1] </span></td></tr> | + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3fju FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fju OCA], [http://pdbe.org/3fju PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fju RCSB], [http://www.ebi.ac.uk/pdbsum/3fju PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fju ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CBPA1_HUMAN CBPA1_HUMAN]] Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro.<ref>PMID:8806703</ref> [[http://www.uniprot.org/uniprot/ICAA_ASCSU ICAA_ASCSU]] Inhibits carboxypeptidase A. | + | [https://www.uniprot.org/uniprot/CBPA1_HUMAN CBPA1_HUMAN] Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro.<ref>PMID:8806703</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fj/3fju_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fj/3fju_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | ==See Also== | | ==See Also== |
| - | *[[Carboxypeptidase|Carboxypeptidase]] | + | *[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ascsu]] | + | [[Category: Ascaris suum]] |
| - | [[Category: Carboxypeptidase A]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Arolas, J L]] | + | [[Category: Arolas JL]] |
| - | [[Category: Aviles, F X]] | + | [[Category: Aviles FX]] |
| - | [[Category: Gomis-Ruth, F X]] | + | [[Category: Gomis-Ruth FX]] |
| - | [[Category: Huber, R]] | + | [[Category: Huber R]] |
| - | [[Category: Sanglas, L]] | + | [[Category: Sanglas L]] |
| - | [[Category: Ascariasis]]
| + | |
| - | [[Category: Carboxypeptidase]]
| + | |
| - | [[Category: Host resistance]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Immunolocalization]]
| + | |
| - | [[Category: Metal-binding]]
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| - | [[Category: Metallocarboxypeptidase inhibitor]]
| + | |
| - | [[Category: Metalloenzyme inhibitor]]
| + | |
| - | [[Category: Metalloprotease]]
| + | |
| - | [[Category: Metalloprotease inhibitor]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Protease inhibitor]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Zymogen]]
| + | |
| Structural highlights
Function
CBPA1_HUMAN Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro.[1]
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 PubMed
Roundworms of the genus Ascaris are common parasites of the human gastrointestinal tract. A battery of selective inhibitors protects them from host enzymes and the immune system. Here, a metallocarboxypeptidase (MCP) inhibitor, ACI, was identified in protein extracts from Ascaris by intensity-fading MALDI-TOF mass spectrometry. The 67-residue amino acid sequence of ACI showed no significant homology with any known protein. Heterologous overexpression and purification of ACI rendered a functional molecule with nanomolar equilibrium dissociation constants against MCPs, which denoted a preference for digestive and mast cell A/B-type MCPs. Western blotting and immunohistochemistry located ACI in the body wall, intestine, female reproductive tract, and fertilized eggs of Ascaris, in accordance with its target specificity. The crystal structure of the complex of ACI with human carboxypeptidase A1, one of its potential targets in vivo, revealed a protein with a fold consisting of two tandem homologous domains, each containing a beta-ribbon and two disulfide bonds. These domains are connected by an alpha-helical segment and a fifth disulfide bond. Binding and inhibition are exerted by the C-terminal tail, which enters the funnel-like active-site cavity of the enzyme and approaches the catalytic zinc ion. The findings reported provide a basis for the biological function of ACI, which may be essential for parasitic survival during infection.
Mammalian metallopeptidase inhibition at the defense barrier of Ascaris parasite.,Sanglas L, Aviles FX, Huber R, Gomis-Ruth FX, Arolas JL Proc Natl Acad Sci U S A. 2009 Jan 28. PMID:19179285[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Laethem RM, Blumenkopf TA, Cory M, Elwell L, Moxham CP, Ray PH, Walton LM, Smith GK. Expression and characterization of human pancreatic preprocarboxypeptidase A1 and preprocarboxypeptidase A2. Arch Biochem Biophys. 1996 Aug 1;332(1):8-18. PMID:8806703 doi:http://dx.doi.org/S0003-9861(96)90310-0
- ↑ Sanglas L, Aviles FX, Huber R, Gomis-Ruth FX, Arolas JL. Mammalian metallopeptidase inhibition at the defense barrier of Ascaris parasite. Proc Natl Acad Sci U S A. 2009 Jan 28. PMID:19179285
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