1fq7: Difference between revisions
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[[Image:1fq7.jpg|left|200px]] | [[Image:1fq7.jpg|left|200px]] | ||
'''X-RAY STRUCTURE OF INHIBITOR CP-72,647 BOUND TO SACCHAROPEPSIN''' | {{Structure | ||
|PDB= 1fq7 |SIZE=350|CAPTION= <scene name='initialview01'>1fq7</scene>, resolution 2.8Å | |||
|SITE= | |||
|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> | |||
|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] | |||
|GENE= | |||
}} | |||
'''X-RAY STRUCTURE OF INHIBITOR CP-72,647 BOUND TO SACCHAROPEPSIN''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1FQ7 is a [ | 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== | ||
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:// | 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]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:12:31 2008'' | ||
Revision as of 12:12, 20 March 2008
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| , resolution 2.8Å | |||||||
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| 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
OverviewOverview
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 StructureAbout this Structure
1FQ7 is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
ReferenceReference
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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