1pjp: Difference between revisions
New page: left|200px<br /> <applet load="1pjp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pjp, resolution 2.2Å" /> '''THE 2.2 A CRYSTAL ST... |
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== | ==THE 2.2 A CRYSTAL STRUCTURE OF HUMAN CHYMASE IN COMPLEX WITH SUCCINYL-ALA-ALA-PRO-PHE-CHLOROMETHYLKETONE== | ||
Human chymase (HC) is a chymotrypsin-like serine proteinase expressed by | <StructureSection load='1pjp' size='340' side='right'caption='[[1pjp]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1pjp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PJP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PJP 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]] 2.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=HPH:(2S)-2-AMINO-3-PHENYLPROPANE-1,1-DIOL'>HPH</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</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=1pjp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pjp OCA], [https://pdbe.org/1pjp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pjp RCSB], [https://www.ebi.ac.uk/pdbsum/1pjp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pjp ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CMA1_HUMAN CMA1_HUMAN] Major secreted protease of mast cells with suspected roles in vasoactive peptide generation, extracellular matrix degradation, and regulation of gland secretion. | |||
== 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/1pjp_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=1pjp ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human chymase (HC) is a chymotrypsin-like serine proteinase expressed by mast cells. The 2.2 A crystal structure of HC complexed to the peptidyl inhibitor, succinyl-Ala-Ala-Pro-Phe-chloromethylketone (CMK), was solved and refined to a crystallographic R-factor of 18.4 %. The HC structure exhibits the typical folding pattern of a chymotrypsin-like serine proteinase, and shows particularly similarity to rat chymase 2 (rat mast cell proteinase II) and human cathepsin G. The peptidyl-CMK inhibitor is covalently bound to the active-site residues Ser195 and His57; the peptidyl moiety juxtaposes the S1 entrance frame segment 214-217 by forming a short antiparallel beta-sheet. HC is a highly efficient angiotensin-converting enzyme. Modeling of the chymase-angiotensin I interaction guided by the geometry of the bound chloromethylketone inhibitor indicates that the extended substrate binding site contains features that may generate the dipeptidyl carboxypeptidase-like activity needed for efficient cleavage and activation of the hormone. The C-terminal carboxylate group of angiotensin I docked into the active-site cleft, with the last two residues extending beyond the active site, is perfectly localized to make a favorable hydrogen bond and salt bridge with the amide nitrogen of the Lys40-Phe41 peptide bond and with the epsilon-ammonium group of the Lys40 side-chain. This amide positioning is unique to the chymase-related proteinases, and only chymases from primates possess a Lys residue at position 40. Thus, the structure conveniently explains the preferred conversion of angiotensin I to angiotensin II by human chymase. | |||
The 2.2 A crystal structure of human chymase in complex with succinyl-Ala-Ala-Pro-Phe-chloromethylketone: structural explanation for its dipeptidyl carboxypeptidase specificity.,Pereira PJ, Wang ZM, Rubin H, Huber R, Bode W, Schechter NM, Strobl S J Mol Biol. 1999 Feb 12;286(1):163-73. PMID:9931257<ref>PMID:9931257</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1pjp" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bode | [[Category: Bode W]] | ||
[[Category: Huber | [[Category: Huber R]] | ||
[[Category: Pereira | [[Category: Pereira PJB]] | ||
[[Category: Rubin | [[Category: Rubin H]] | ||
[[Category: Schechter | [[Category: Schechter NM]] | ||
[[Category: Strobl | [[Category: Strobl S]] | ||
[[Category: Wang | [[Category: Wang ZM]] | ||
