2pj6: Difference between revisions

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-{{Seed}}
-[[Image:2pj6.png|left|200px]]
-<!--
+==CRYSTAL STRUCTURE OF ACTIVATED PORCINE PANCREATIC CARBOXYPEPTIDASE B 2-(3-Aminomethyl-phenyl)-3-{hydroxy-[(R)-2-methyl-1-(2-phenyl-ethanesulfonylamino)-propyl]-phosphinoyl}-propionic acid COMPLEX==
-The line below this paragraph, containing "STRUCTURE_2pj6", creates the "Structure Box" on the page.
+<StructureSection load='2pj6' size='340' side='right'caption='[[2pj6]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2pj6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PJ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PJ6 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</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=059:(2S)-2-[3-(AMINOMETHYL)PHENYL]-3-{(S)-HYDROXY[(1R)-2-METHYL-1-{[(2-PHENYLETHYL)SULFONYL]AMINO}PROPYL]PHOSPHORYL}PROPANOIC+ACID'>059</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_2pj6|  PDB=2pj6  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pj6 OCA], [https://pdbe.org/2pj6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pj6 RCSB], [https://www.ebi.ac.uk/pdbsum/2pj6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pj6 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CBPB1_PIG CBPB1_PIG]
+== 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/pj/2pj6_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2pj6 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+This article reports the crystal structures of inhibitors of the functional form of thrombin-activatable fibrinolysis inhibitor (TAFIa). In vivo experiments indicate that selective inhibitors of TAFIa would be useful in the treatment of heart attacks. Since TAFIa rapidly degrades in solution, the homologous protein porcine pancreatic carboxypeptidase B (pp-CpB) was used in these crystallography studies. Both TAFIa and pp-CpB are zinc-based exopeptidases that are specific for basic residues. The final development candidate, BX 528, is a potent inhibitor of TAFIa (2 nM) and has almost no measurable effect on the major selectivity target, carboxypeptidase N. BX 528 was designed to mimic the tripeptide Phe-Val-Lys. A sulfonamide replaces the Phe-Val amide bond and a phosphinate connects the Val and Lys groups. The phosphinate also chelates the active-site zinc. The electrostatic interactions with the protein mimic those of the natural substrate. The primary amine in BX 528 forms a salt bridge to Asp255 at the base of the S1' pocket. The carboxylic acid interacts with Arg145 and the sulfonamide is hydrogen bonded to Arg71. Isopropyl and phenyl groups replace the side chains of Val and Phe, respectively. A series of structures are presented here that illustrate the evolution of BX 528 from thiol-based inhibitors that mimic a free C-terminal arginine. The first step in development was the replacement of the thiol with a phosphinate. This caused a precipitous drop in binding affinity. Potency was reclaimed by extending the inhibitors into the downstream binding sites for the natural substrate.
-===CRYSTAL STRUCTURE OF ACTIVATED PORCINE PANCREATIC CARBOXYPEPTIDASE B 2-(3-Aminomethyl-phenyl)-3-{hydroxy-[(R)-2-methyl-1-(2-phenyl-ethanesulfonylamino)-propyl]-phosphinoyl}-propionic acid COMPLEX===
+Structures of potent selective peptide mimetics bound to carboxypeptidase B.,Adler M, Buckman B, Bryant J, Chang Z, Chu K, Emayan K, Hrvatin P, Islam I, Morser J, Sukovich D, West C, Yuan S, Whitlow M Acta Crystallogr D Biol Crystallogr. 2008 Feb;64(Pt 2):149-57. Epub 2008, Jan 16. PMID:18219114<ref>PMID:18219114</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2pj6" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_18219114}}, adds the Publication Abstract to the page
+*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 18219114 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_18219114}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Large Structures]]
-PJ6 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PJ6 OCA].
-==Reference==
-Structures of potent selective peptide mimetics bound to carboxypeptidase B., Adler M, Buckman B, Bryant J, Chang Z, Chu K, Emayan K, Hrvatin P, Islam I, Morser J, Sukovich D, West C, Yuan S, Whitlow M, Acta Crystallogr D Biol Crystallogr. 2008 Feb;64(Pt 2):149-57. Epub 2008, Jan 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18219114 18219114]
-[[Category: Carboxypeptidase B]]
-[[Category: Single protein]]
 [[Category: Sus scrofa]]
-[[Category: Adler, M.]]
+[[Category: Adler M]]
-[[Category: Whitlow, M.]]
+[[Category: Whitlow M]]
-[[Category: Carboxypeptidase b]]
-[[Category: Exopeptidase]]
-[[Category: Hydrolase]]
-[[Category: Phosphinate based inhibitor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 12:14:23 2008''