1mhw
From Proteopedia
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|PDB= 1mhw |SIZE=350|CAPTION= <scene name='initialview01'>1mhw</scene>, resolution 1.9Å | |PDB= 1mhw |SIZE=350|CAPTION= <scene name='initialview01'>1mhw</scene>, resolution 1.9Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=BP4:BIPHENYL-4-YL-ACETALDEHYDE'>BP4</scene>, <scene name='pdbligand=CSW:CYSTEINE-S-DIOXIDE'>CSW</scene>, <scene name='pdbligand=DAR:D-ARGININE'>DAR</scene>, <scene name='pdbligand=PEA:2-PHENYLETHYLAMINE'>PEA</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Cathepsin_L Cathepsin L], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.15 3.4.22.15] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_L Cathepsin L], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.15 3.4.22.15] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1cjl|1CJL]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mhw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mhw OCA], [http://www.ebi.ac.uk/pdbsum/1mhw PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1mhw RCSB]</span> | ||
}} | }} | ||
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[[Category: x-ray structure]] | [[Category: x-ray structure]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:16:14 2008'' |
Revision as of 19:16, 30 March 2008
| |||||||
| , resolution 1.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Activity: | Cathepsin L, with EC number 3.4.22.15 | ||||||
| Related: | 1CJL
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Design of non-covalent inhibitors of human cathepsin L. From the 96-residue proregion to optimized tripeptides
Overview
A novel series of noncovalent inhibitors of cathepsin L have been designed to mimic the mode of autoinhibition of procathepsin L. Just like the propeptide, these peptide-based inhibitors have a reverse-binding mode relative to a substrate and span both the S' and S subsites of the enzyme active site. In contrast to previous studies in which even moderate truncation of the full-length propeptide led to rapid reduction in potency, these blocked tripeptide-sized inhibitors maintain nanomolar potency. Moreover, these short peptides show higher selectivity (up to 310-fold) for inhibiting cathepsin L over K versus only 2-fold selectivity of the 96-residue propeptide of cathepsin L. A 1.9 A X-ray crystallographic structure of the complex of cathepsin L with one of the inhibitors confirms the designed reverse-binding mode of the inhibitor as well as its noncovalent nature. Enzymatic analysis also shows the inhibitors to be resistant to hydrolysis at elevated concentrations of the enzyme. The mode of inhibition of these molecules provides a general strategy for inhibiting other cathepsins as well as other proteases.
About this Structure
1MHW is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Design of noncovalent inhibitors of human cathepsin L. From the 96-residue proregion to optimized tripeptides., Chowdhury SF, Sivaraman J, Wang J, Devanathan G, Lachance P, Qi H, Menard R, Lefebvre J, Konishi Y, Cygler M, Sulea T, Purisima EO, J Med Chem. 2002 Nov 21;45(24):5321-9. PMID:12431059
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