1fq7

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[[Image:1fq7.jpg|left|200px]]<br /><applet load="1fq7" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1fq7.jpg|left|200px]]
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caption="1fq7, resolution 2.8&Aring;" />
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'''X-RAY STRUCTURE OF INHIBITOR CP-72,647 BOUND TO SACCHAROPEPSIN'''<br />
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{{Structure
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|PDB= 1fq7 |SIZE=350|CAPTION= <scene name='initialview01'>1fq7</scene>, resolution 2.8&Aring;
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|SITE=
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|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>
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|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]
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|GENE=
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}}
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'''X-RAY STRUCTURE OF INHIBITOR CP-72,647 BOUND TO SACCHAROPEPSIN'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1FQ7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=BOC:'>BOC</scene>, <scene name='pdbligand=PHE:'>PHE</scene>, <scene name='pdbligand=HIS:'>HIS</scene>, <scene name='pdbligand=CAL:'>CAL</scene> and <scene name='pdbligand=NME:'>NME</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FQ7 OCA].
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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].
==Reference==
==Reference==
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=11061973 11061973]
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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: Saccharomyces cerevisiae]]
[[Category: Saccharopepsin]]
[[Category: Saccharopepsin]]
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[[Category: t-boc terminal group]]
[[Category: t-boc terminal group]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:41:26 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:12:31 2008''

Revision as of 09:12, 20 March 2008

Image:1fq7.jpg


PDB ID 1fq7

Drag the structure with the mouse to rotate
, resolution 2.8Å
Ligands: , , , , and
Activity: Saccharopepsin, with EC number 3.4.23.25
Coordinates: save as pdb, mmCIF, xml



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


Overview

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

1FQ7 is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from 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:11061973

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