2bo9: Difference between revisions

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-[[Image:2bo9.gif|left|200px]]<br /><applet load="2bo9" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="2bo9, resolution 1.60&Aring;" />
-'''HUMAN CARBOXYPEPTIDASE A4 IN COMPLEX WITH HUMAN LATEXIN.'''<br />
-==Overview==
+==Human carboxypeptidase A4 in complex with human latexin.==
-The only endogenous protein inhibitor known for metallocarboxypeptidases (MCPs) is latexin, a 25-kDa protein discovered in the rat brain. Latexin, alias endogenous carboxypeptidase inhibitor, inhibits human CPA4 (hCPA4), whose expression is induced in prostate cancer cells after treatment with histone deacetylase inhibitors. hCPA4 is a member of the A/B subfamily of MCPs and displays the characteristic alpha/beta-hydrolase fold. Human latexin consists of two topologically equivalent subdomains, reminiscent of cystatins, consisting of an alpha-helix enveloped by a curved beta-sheet. These subdomains are packed against each other through the helices and linked by a connecting segment encompassing a third alpha-helix. The enzyme is bound at the interface of these subdomains. The complex occludes a large contact surface but makes rather few contacts, despite a nanomolar inhibition constant. This low specificity explains the flexibility of latexin in inhibiting all vertebrate A/B MCPs tested, even across species barriers. In contrast, modeling studies reveal why the N/E subfamily of MCPs and invertebrate A/B MCPs are not inhibited. Major differences in the loop segments shaping the border of the funnel-like access to the protease active site impede complex formation with latexin. Several sequences ascribable to diverse tissues and organs have been identified in vertebrate genomes as being highly similar to latexin. They are proposed to constitute the latexin family of potential inhibitors. Because they are ubiquitous, latexins could represent for vertebrate A/B MCPs the counterparts of tissue inhibitors of metalloproteases for matrix metalloproteinases.
+<StructureSection load='2bo9' size='340' side='right'caption='[[2bo9]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2bo9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2bk7 2bk7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BO9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BO9 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]] 1.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACN:ACETONE'>ACN</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=VAL:VALINE'>VAL</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=2bo9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bo9 OCA], [https://pdbe.org/2bo9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bo9 RCSB], [https://www.ebi.ac.uk/pdbsum/2bo9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bo9 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CBPA4_HUMAN CBPA4_HUMAN] Metalloprotease that could be involved in the histone hyperacetylation pathway.<ref>PMID:10383164</ref>
+== 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/bo/2bo9_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=2bo9 ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-BO9 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=VAL:'>VAL</scene>, <scene name='pdbligand=MPD:'>MPD</scene> and <scene name='pdbligand=ACN:'>ACN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 2BK7. Known structural/functional Site: <scene name='pdbsite=AC1:Acn+Binding+Site+For+Chain+L'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BO9 OCA].
+*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
+== References ==
-==Reference==
+<references/>
-Structure of human carboxypeptidase A4 with its endogenous protein inhibitor, latexin., Pallares I, Bonet R, Garcia-Castellanos R, Ventura S, Aviles FX, Vendrell J, Gomis-Ruth FX, Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):3978-83. Epub 2005 Feb 28. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15738388 15738388]
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Aviles, F X.]]
+[[Category: Aviles FX]]
-[[Category: Bonet, R.]]
+[[Category: Bonet R]]
-[[Category: Garcia-Castellanos, R.]]
+[[Category: Garcia-Castellanos R]]
-[[Category: Gomis-Rueth, F X.]]
+[[Category: Gomis-Rueth FX]]
-[[Category: Pallares, I.]]
+[[Category: Pallares I]]
-[[Category: Vendrell, J.]]
+[[Category: Vendrell J]]
-[[Category: Ventura, S.]]
+[[Category: Ventura S]]
-[[Category: ACN]]
-[[Category: MPD]]
-[[Category: NAG]]
-[[Category: VAL]]
-[[Category: ZN]]
-[[Category: endogenous protein inhibitor]]
-[[Category: hydrolase]]
-[[Category: latexin]]
-[[Category: metallocarboxypeptidase]]
-[[Category: metalloprotease carboxypeptidase]]
-[[Category: x-ray crystal structure]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:39:50 2008''