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2hhn

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(New page: 200px<br /> <applet load="2hhn" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hhn, resolution 1.55&Aring;" /> '''Cathepsin S in comp...)
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[[Image:2hhn.gif|left|200px]]<br />
 
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<applet load="2hhn" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2hhn, resolution 1.55&Aring;" />
 
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'''Cathepsin S in complex with non covalent arylaminoethyl amide.'''<br />
 
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==Overview==
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==Cathepsin S in complex with non covalent arylaminoethyl amide.==
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The synthesis and structure-activity relationship of a series of, arylaminoethyl amide cathepsin S inhibitors are reported. Optimization of, P3 and P2 groups to improve overall physicochemical properties resulted in, significant improvements in oral bioavailability over early lead, compounds. An X-ray structure of compound 37 bound to the active site of, cathepsin S is also reported.
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<StructureSection load='2hhn' size='340' side='right'caption='[[2hhn]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2hhn]] 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=2HHN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HHN FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNQ:N-[(1R)-1-[(BENZYLSULFONYL)METHYL]-2-{[(1S)-1-METHYL-2-{[4-(TRIFLUOROMETHOXY)PHENYL]AMINO}ETHYL]AMINO}-2-OXOETHYL]MORPHOLINE-4-CARBOXAMIDE'>GNQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hhn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hhn OCA], [https://pdbe.org/2hhn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hhn RCSB], [https://www.ebi.ac.uk/pdbsum/2hhn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hhn ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CATS_HUMAN CATS_HUMAN] Thiol protease. Key protease responsible for the removal of the invariant chain from MHC class II molecules. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin L and cathepsin N.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hh/2hhn_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2hhn ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The synthesis and structure-activity relationship of a series of arylaminoethyl amide cathepsin S inhibitors are reported. Optimization of P3 and P2 groups to improve overall physicochemical properties resulted in significant improvements in oral bioavailability over early lead compounds. An X-ray structure of compound 37 bound to the active site of cathepsin S is also reported.
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==About this Structure==
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Synthesis and SAR of arylaminoethyl amides as noncovalent inhibitors of cathepsin S: P3 cyclic ethers.,Tully DC, Liu H, Chatterjee AK, Alper PB, Epple R, Williams JA, Roberts MJ, Woodmansee DH, Masick BT, Tumanut C, Li J, Spraggon G, Hornsby M, Chang J, Tuntland T, Hollenbeck T, Gordon P, Harris JL, Karanewsky DS Bioorg Med Chem Lett. 2006 Oct 1;16(19):5112-7. Epub 2006 Jul 28. PMID:16876402<ref>PMID:16876402</ref>
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2HHN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and GNQ as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cathepsin_S Cathepsin S], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.27 3.4.22.27] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2HHN OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Synthesis and SAR of arylaminoethyl amides as noncovalent inhibitors of cathepsin S: P3 cyclic ethers., Tully DC, Liu H, Chatterjee AK, Alper PB, Epple R, Williams JA, Roberts MJ, Woodmansee DH, Masick BT, Tumanut C, Li J, Spraggon G, Hornsby M, Chang J, Tuntland T, Hollenbeck T, Gordon P, Harris JL, Karanewsky DS, Bioorg Med Chem Lett. 2006 Oct 1;16(19):5112-7. Epub 2006 Jul 28. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16876402 16876402]
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</div>
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[[Category: Cathepsin S]]
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<div class="pdbe-citations 2hhn" style="background-color:#fffaf0;"></div>
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[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Clark, K.]]
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[[Category: Harris, J.L.]]
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[[Category: Hornsby, M.]]
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[[Category: Karenewsky, D.S.]]
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[[Category: Kulathila, R.]]
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[[Category: Lesley, S.A.]]
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[[Category: Spraggon, G.]]
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[[Category: Tully, D.C.]]
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[[Category: GNQ]]
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[[Category: SO4]]
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[[Category: arylaminoethyl amide]]
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[[Category: cathepsin s]]
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[[Category: inhibition]]
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[[Category: noncovalent]]
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[[Category: protease]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:32:50 2007''
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==See Also==
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*[[Cathepsin 3D structures|Cathepsin 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Clark K]]
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[[Category: Harris JL]]
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[[Category: Hornsby M]]
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[[Category: Karenewsky DS]]
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[[Category: Kulathila R]]
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[[Category: Lesley SA]]
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[[Category: Spraggon G]]
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[[Category: Tully DC]]

Current revision

Cathepsin S in complex with non covalent arylaminoethyl amide.

PDB ID 2hhn

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