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1fq7

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X-RAY STRUCTURE OF INHIBITOR CP-72,647 BOUND TO SACCHAROPEPSIN

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Retrieved from "http://52.214.119.220/wiki/index.php/1fq7"

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-[[Image:1fq7.jpg|left|200px]]
- {{Structure
+==X-RAY STRUCTURE OF INHIBITOR CP-72,647 BOUND TO SACCHAROPEPSIN==
-|PDB= 1fq7 |SIZE=350|CAPTION= <scene name='initialview01'>1fq7</scene>, resolution 2.8&Aring;
+<StructureSection load='1fq7' size='340' side='right'caption='[[1fq7]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=BOC:TERT-BUTYL+HYDROGEN+CARBONATE'>BOC</scene>, <scene name='pdbligand=PHE:PHENYLALANINE'>PHE</scene>, <scene name='pdbligand=HIS:HISTIDINE'>HIS</scene>, <scene name='pdbligand=CAL:5-AMINO-6-CYCLOHEXYL-4-HYDROXY-2-ISOBUTYL-HEXANOIC+ACID'>CAL</scene> and <scene name='pdbligand=NME:METHYLAMINE'>NME</scene>
+<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>
-|ACTIVITY= [http://en.wikipedia.org/wiki/Saccharopepsin Saccharopepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.25 3.4.23.25]
+</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>
-|GENE=
+<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/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=1fq7 ConSurf].
+<div style="clear:both"></div>
-'''X-RAY STRUCTURE OF INHIBITOR CP-72,647 BOUND TO SACCHAROPEPSIN'''
+==See Also==
+*[[Pepsin|Pepsin]]
+*[[Proteinase 3D structures|Proteinase 3D structures]]
-==Overview==
+__TOC__
-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.
+</StructureSection>
+[[Category: Large Structures]]
-==About this Structure==
-FQ7 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].
-==Reference==
-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]
 [[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: BOC]]
-[[Category: CAL]]
-[[Category: HIS]]
-[[Category: NAG]]
-[[Category: NME]]
-[[Category: PHE]]
-[[Category: hydrophobic inhibitor]]
-[[Category: t-boc terminal group]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:12:31 2008''

1fq7

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X-RAY STRUCTURE OF INHIBITOR CP-72,647 BOUND TO SACCHAROPEPSIN

Structural highlights

Function

Evolutionary Conservation

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