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[[Image:1fq7.jpg|left|200px]]
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{{STRUCTURE_1fq7|  PDB=1fq7  |  SCENE=  }}
'''X-RAY STRUCTURE OF INHIBITOR CP-72,647 BOUND TO SACCHAROPEPSIN'''


==X-RAY STRUCTURE OF INHIBITOR CP-72,647 BOUND TO SACCHAROPEPSIN==
<StructureSection load='1fq7' size='340' side='right'caption='[[1fq7]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1fq7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FQ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FQ7 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2Y3:N-(TERT-BUTOXYCARBONYL)-L-PHENYLALANYL-N-[(2S,3S,5R)-1-CYCLOHEXYL-3-HYDROXY-7-METHYL-5-(METHYLCARBAMOYL)OCTAN-2-YL]-L-HISTIDINAMIDE'>2Y3</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=KBG:2-KETO-BETA-D-GLUCOSE'>KBG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=1fq7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fq7 OCA], [https://pdbe.org/1fq7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fq7 RCSB], [https://www.ebi.ac.uk/pdbsum/1fq7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fq7 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CARP_YEAST CARP_YEAST] Aspartyl protease implicated in the post-translational regulation of S.cerevisiae vacuolar proteinases. Acts on YSCB, on YSCY and on itself.
== 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/fq/1fq7_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=1fq7 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Saccharopepsin is a vacuolar aspartic proteinase involved in activation of a number of hydrolases. The enzyme has great structural homology to mammalian aspartic proteinases including human renin and we have used it as a model system to study the binding of renin inhibitors by X-ray crystallography. Five medium-to-high resolution structures of saccharopepsin complexed with transition-state analogue renin inhibitors were determined. The structure of a cyclic peptide inhibitor (PD-129,541) complexed with the proteinase was solved to 2.5 A resolution. This inhibitor has low affinity for human renin yet binds very tightly to the yeast proteinase (K(i)=4 nM). The high affinity of this inhibitor can be attributed to its bulky cyclic moiety spanning P(2)-P(3)' and other residues that appear to optimally fit the binding sub-sites of the enzyme. Superposition of the saccharopepsin structure on that of renin showed that a movement of the loop 286-301 relative to renin facilitates tighter binding of this inhibitor to saccharopepsin. Our 2.8 A resolution structure of the complex with CP-108,420 shows that its benzimidazole P(3 )replacement retains one of the standard hydrogen bonds that normally involve the inhibitor's main-chain. This suggests a non-peptide lead in overcoming the problem of susceptible peptide bonds in the design of aspartic proteinase inhibitors. CP-72,647 which possesses a basic histidine residue at P(2), has a high affinity for renin (K(i)=5 nM) but proves to be a poor inhibitor for saccharopepsin (K(i)=3.7 microM). This may stem from the fact that the histidine residue would not bind favourably with the predominantly hydrophobic S(2) sub-site of saccharopepsin.


==Overview==
X-ray structures of five renin inhibitors bound to saccharopepsin: exploration of active-site specificity.,Cronin NB, Badasso MO, J Tickle I, Dreyer T, Hoover DJ, Rosati RL, Humblet CC, Lunney EA, Cooper JB J Mol Biol. 2000 Nov 10;303(5):745-60. PMID:11061973<ref>PMID:11061973</ref>
Saccharopepsin is a vacuolar aspartic proteinase involved in activation of a number of hydrolases. The enzyme has great structural homology to mammalian aspartic proteinases including human renin and we have used it as a model system to study the binding of renin inhibitors by X-ray crystallography. Five medium-to-high resolution structures of saccharopepsin complexed with transition-state analogue renin inhibitors were determined. The structure of a cyclic peptide inhibitor (PD-129,541) complexed with the proteinase was solved to 2.5 A resolution. This inhibitor has low affinity for human renin yet binds very tightly to the yeast proteinase (K(i)=4 nM). The high affinity of this inhibitor can be attributed to its bulky cyclic moiety spanning P(2)-P(3)' and other residues that appear to optimally fit the binding sub-sites of the enzyme. Superposition of the saccharopepsin structure on that of renin showed that a movement of the loop 286-301 relative to renin facilitates tighter binding of this inhibitor to saccharopepsin. Our 2.8 A resolution structure of the complex with CP-108,420 shows that its benzimidazole P(3 )replacement retains one of the standard hydrogen bonds that normally involve the inhibitor's main-chain. This suggests a non-peptide lead in overcoming the problem of susceptible peptide bonds in the design of aspartic proteinase inhibitors. CP-72,647 which possesses a basic histidine residue at P(2), has a high affinity for renin (K(i)=5 nM) but proves to be a poor inhibitor for saccharopepsin (K(i)=3.7 microM). This may stem from the fact that the histidine residue would not bind favourably with the predominantly hydrophobic S(2) sub-site of saccharopepsin.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1FQ7 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FQ7 OCA].
</div>
<div class="pdbe-citations 1fq7" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
X-ray structures of five renin inhibitors bound to saccharopepsin: exploration of active-site specificity., Cronin NB, Badasso MO, J Tickle I, Dreyer T, Hoover DJ, Rosati RL, Humblet CC, Lunney EA, Cooper JB, J Mol Biol. 2000 Nov 10;303(5):745-60. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11061973 11061973]
*[[Pepsin|Pepsin]]
*[[Proteinase 3D structures|Proteinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharopepsin]]
[[Category: Badasso MO]]
[[Category: Single protein]]
[[Category: Cooper JB]]
[[Category: Badasso, M O.]]
[[Category: Cronin NB]]
[[Category: Cooper, J B.]]
[[Category: Dreyer T]]
[[Category: Cronin, N B.]]
[[Category: Hoover DJ]]
[[Category: Dreyer, T.]]
[[Category: Humblet CC]]
[[Category: Hoover, D J.]]
[[Category: Lunney EA]]
[[Category: Humblet, C C.]]
[[Category: Rosati RL]]
[[Category: Lunney, E A.]]
[[Category: Tickle IJ]]
[[Category: Rosati, R L.]]
[[Category: Tickle, I J.]]
[[Category: Hydrophobic inhibitor]]
[[Category: T-boc terminal group]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 16:38:07 2008''
Retrieved from "https://proteopedia.org/1fq7"