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New page: left|200px<br /><applet load="1sp4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sp4, resolution 2.20Å" /> '''Crystal structure of...
 
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[[Image:1sp4.jpg|left|200px]]<br /><applet load="1sp4" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1sp4, resolution 2.20&Aring;" />
'''Crystal structure of NS-134 in complex with bovine cathepsin B: a two headed epoxysuccinyl inhibitor extends along the whole active site cleft'''<br />


==Overview==
==Crystal structure of NS-134 in complex with bovine cathepsin B: a two headed epoxysuccinyl inhibitor extends along the whole active site cleft==
The crystal structure of the inhibitor NS-134 in complex with bovine, cathepsin B reveals that functional groups attached to both sides of the, epoxysuccinyl reactive group bind to the part of active-site cleft as, predicted. The -Leu-Pro-OH side binds to the primed binding sites, interacting with the His110 and His111 residues with its C-terminal, carboxy group, whereas the -Leu-Gly-Meu (-Leu-Gly-Gly-OMe) part (Meu, methoxycarbonylmethyl) binds along the non-primed binding sites., Comparison with the propeptide structures of cathepsins revealed that the, binding of the latter part is least similar to the procathepsin B, structure; this result, together with the two-residue shift in positioning, of the Leu-Gly-Gly part, suggests that the propeptide structures of the, cognate enzymes may not be the best starting point for the design of, reverse binding inhibitors.
<StructureSection load='1sp4' size='340' side='right'caption='[[1sp4]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1sp4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SP4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SP4 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EP2:METHYL+N-[(2S)-4-{[(1S)-1-{[(2S)-2-CARBOXYPYRROLIDIN-1-YL]CARBONYL}-3-METHYLBUTYL]AMINO}-2-HYDROXY-4-OXOBUTANOYL]-L-LEUCYLGLYCYLGLYCINATE'>EP2</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=1sp4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sp4 OCA], [https://pdbe.org/1sp4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sp4 RCSB], [https://www.ebi.ac.uk/pdbsum/1sp4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sp4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CATB_BOVIN CATB_BOVIN] Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis.
== 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/sp/1sp4_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=1sp4 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The crystal structure of the inhibitor NS-134 in complex with bovine cathepsin B reveals that functional groups attached to both sides of the epoxysuccinyl reactive group bind to the part of active-site cleft as predicted. The -Leu-Pro-OH side binds to the primed binding sites interacting with the His110 and His111 residues with its C-terminal carboxy group, whereas the -Leu-Gly-Meu (-Leu-Gly-Gly-OMe) part (Meu, methoxycarbonylmethyl) binds along the non-primed binding sites. Comparison with the propeptide structures of cathepsins revealed that the binding of the latter part is least similar to the procathepsin B structure; this result, together with the two-residue shift in positioning of the Leu-Gly-Gly part, suggests that the propeptide structures of the cognate enzymes may not be the best starting point for the design of reverse binding inhibitors.


==About this Structure==
Crystal structure of NS-134 in complex with bovine cathepsin B: a two-headed epoxysuccinyl inhibitor extends along the entire active-site cleft.,Stern I, Schaschke N, Moroder L, Turk D Biochem J. 2004 Jul 15;381(Pt 2):511-7. PMID:15084146<ref>PMID:15084146</ref>
1SP4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with EPO, LEU and PRO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cathepsin_B Cathepsin B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.1 3.4.22.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1SP4 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Crystal structure of NS-134 in complex with bovine cathepsin B: a two-headed epoxysuccinyl inhibitor extends along the entire active-site cleft., Stern I, Schaschke N, Moroder L, Turk D, Biochem J. 2004 Jul 15;381(Pt 2):511-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15084146 15084146]
</div>
<div class="pdbe-citations 1sp4" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Cathepsin 3D structures|Cathepsin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Cathepsin B]]
[[Category: Large Structures]]
[[Category: Protein complex]]
[[Category: Moroder L]]
[[Category: Moroder, L.]]
[[Category: Schaschke N]]
[[Category: Schaschke, N.]]
[[Category: Stern I]]
[[Category: Stern, I.]]
[[Category: Turk D]]
[[Category: Turk, D.]]
[[Category: EPO]]
[[Category: LEU]]
[[Category: PRO]]
[[Category: cathepsin b]]
[[Category: epoxysuccinyl-based inhibitors]]
[[Category: inhibitor design]]
 
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