View source for 2hvx


==Discovery of Potent, Orally Active, Nonpeptide Inhibitors of Human Mast Cell Chymase by Using Structure-Based Drug Design==
<StructureSection load='2hvx' size='340' side='right'caption='[[2hvx]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2hvx]] is a 1 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=2HVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HVX 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DRX:[(1S)-1-(5-CHLORO-1-BENZOTHIEN-3-YL)-2-(2-NAPHTHYLAMINO)-2-OXOETHYL]PHOSPHONIC+ACID'>DRX</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=2hvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hvx OCA], [https://pdbe.org/2hvx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hvx RCSB], [https://www.ebi.ac.uk/pdbsum/2hvx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hvx 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/hv/2hvx_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=2hvx ConSurf].
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== Publication Abstract from PubMed ==
A series of beta-carboxamido-phosphon(in)ic acids (2) was identified as a new structural motif for obtaining potent inhibitors of human mast cell chymase. For example, 1-naphthyl derivative 5f had an IC50 value of 29 nM and (E)-styryl derivative 6g had an IC50 value of 3.5 nM. An X-ray structure for 5f.chymase revealed key interactions within the enzyme active site. Compound 5f was selective for inhibiting chymase versus eight serine proteases. Compound 6h was orally bioavailable in rats (F=39%), and orally efficacious in a hamster model of inflammation.

Discovery of potent, selective, orally active, nonpeptide inhibitors of human mast cell chymase.,Greco MN, Hawkins MJ, Powell ET, Almond HR Jr, de Garavilla L, Hall J, Minor LK, Wang Y, Corcoran TW, Di Cera E, Cantwell AM, Savvides SN, Damiano BP, Maryanoff BE J Med Chem. 2007 Apr 19;50(8):1727-30. Epub 2007 Mar 16. PMID:17361995<ref>PMID:17361995</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2hvx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Almond HR]]
[[Category: Cantwell AM]]
[[Category: Damiano BP]]
[[Category: Di Cera E]]
[[Category: Greco MN]]
[[Category: Hawkins MJ]]
[[Category: Maryanoff BE]]
[[Category: Minor LA]]
[[Category: Powell ET]]
[[Category: Savvides SN]]
[[Category: Wang Y]]
[[Category: Wells GI]]
[[Category: De Garavilla L]]