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| | ==Structure of the complex between SmCI and human carboxypeptidase A4== | | ==Structure of the complex between SmCI and human carboxypeptidase A4== |
| - | <StructureSection load='4bd9' size='340' side='right' caption='[[4bd9]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='4bd9' size='340' side='right'caption='[[4bd9]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4bd9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Feather_duster Feather duster] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BD9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BD9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4bd9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Sabellastarte_magnifica Sabellastarte magnifica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BD9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BD9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2bo9|2bo9]], [[2boa|2boa]], [[4a94|4a94]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4bd9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bd9 OCA], [http://pdbe.org/4bd9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bd9 RCSB], [http://www.ebi.ac.uk/pdbsum/4bd9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bd9 ProSAT]</span></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=4bd9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bd9 OCA], [https://pdbe.org/4bd9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bd9 RCSB], [https://www.ebi.ac.uk/pdbsum/4bd9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bd9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CBPA4_HUMAN CBPA4_HUMAN]] Metalloprotease that could be involved in the histone hyperacetylation pathway.<ref>PMID:10383164</ref> | + | [https://www.uniprot.org/uniprot/CBPA4_HUMAN CBPA4_HUMAN] Metalloprotease that could be involved in the histone hyperacetylation pathway.<ref>PMID:10383164</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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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: Feather duster]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Alonso-del-Ribero, M]] | + | [[Category: Sabellastarte magnifica]] |
| - | [[Category: Aviles, F X]] | + | [[Category: Alonso-del-Ribero M]] |
| - | [[Category: Chavez, M A]] | + | [[Category: Aviles FX]] |
| - | [[Category: Reverter, D]] | + | [[Category: Chavez MA]] |
| - | [[Category: Reytor, M L]] | + | [[Category: Reverter D]] |
| - | [[Category: Trejo, S A]] | + | [[Category: Reytor ML]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | [[Category: Trejo SA]] |
| - | [[Category: Serine protease inhibitor]]
| + | |
| Structural highlights
Function
CBPA4_HUMAN Metalloprotease that could be involved in the histone hyperacetylation pathway.[1]
Publication Abstract from PubMed
The crystal structure of SmCI (Sabellastarte magnifica carboxypeptidase inhibitor) has been determined in complex with human carboxypeptidase A4 (hCPA4). SmCI is composed by three BPTI/Kunitz domains, each one displaying high structural homology and functionality with serine protease inhibitors. Moreover, SmCI possesses a distinctive capability to inhibit metallo-carboxypeptidases, constituting a bifunctional metallocarboxy- and serine protease inhibitor. The structure of the 1:1 complex of SmCI with hCPA4 reveals a noncanonical mechanism of carboxypeptidase inhibition, which surprisingly occurs mainly via the N-terminal segment, which penetrates into the active site groove of the enzyme. Mutagenesis and biochemical analysis confirm the major role of the N-terminal segment in the inhibition of carboxypeptidases. SmCI represents a tri-Kunitz serine protease inhibitor adapted to inhibit metallo-carboxypeptidases and discloses an unusual mechanism of inhibition by the N-terminal segment, emulating the "classical" C-terminal substrate-like inhibition.
A Noncanonical Mechanism of Carboxypeptidase Inhibition Revealed by the Crystal Structure of the Tri-Kunitz SmCI in Complex with Human CPA4.,Alonso Del Rivero M, Reytor ML, Trejo SA, Chavez MA, Aviles FX, Reverter D Structure. 2013 Jul 2;21(7):1118-26. doi: 10.1016/j.str.2013.04.021. Epub 2013, Jun 6. PMID:23746805[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Huang H, Reed CP, Zhang JS, Shridhar V, Wang L, Smith DI. Carboxypeptidase A3 (CPA3): a novel gene highly induced by histone deacetylase inhibitors during differentiation of prostate epithelial cancer cells. Cancer Res. 1999 Jun 15;59(12):2981-8. PMID:10383164
- ↑ Alonso Del Rivero M, Reytor ML, Trejo SA, Chavez MA, Aviles FX, Reverter D. A Noncanonical Mechanism of Carboxypeptidase Inhibition Revealed by the Crystal Structure of the Tri-Kunitz SmCI in Complex with Human CPA4. Structure. 2013 Jul 2;21(7):1118-26. doi: 10.1016/j.str.2013.04.021. Epub 2013, Jun 6. PMID:23746805 doi:10.1016/j.str.2013.04.021
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