3BC3

Exploring inhibitor binding at the S subsites of cathepsin L

Summary for 3BC3

• Entry DOI: 10.2210/pdb3bc3/pdb
• Related: 1MHW
• Descriptor: Cathepsin L heavy and light chains, S-benzyl-N-(biphenyl-4-ylacetyl)-L-cysteinyl-N~5~-(diaminomethyl)-D-ornithyl-N-(2-phenylethyl)-L-tyrosinamide (3 entities in total)
• Functional Keywords: cathepsin l inhibitor binding at the s subsites, glycoprotein, hydrolase, lysosome, protease, thiol protease, zymogen
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: P07711
• Total number of polymer chains: 2
• Total formula weight: 50107.50

Authors

Chowdhury, S.F.,Joseph, L.,Kumar, S.,Tulsidas, S.R.,Bhat, S.,Ziomek, E.,Nard, R.M.,Sivaraman, J.,Purisima, E.O. (deposition date: 2007-11-12, release date: 2008-03-18, Last modification date: 2024-11-13)

Primary citation

Chowdhury, S.F.,Joseph, L.,Kumar, S.,Tulsidas, S.R.,Bhat, S.,Ziomek, E.,Menard, R.,Sivaraman, J.,Purisima, E.O.
Exploring inhibitor binding at the S' subsites of cathepsin L
J.Med.Chem., 51:1361-1368, 2008

PubMed Abstract: We report a series of noncovalent, reversible inhibitors of cathepsin L that have been designed to explore additional binding interactions with the S' subsites. The design was based on our previously reported crystal structure that suggested the possibility of engineering increased interactions with the S' subsites ( Chowdhury et al. J. Med. Chem. 2002, 45, 5321-5329 ). A representative of these new inhibitors has been co-crystallized with mature cathepsin L, and the structure has been solved and refined at 2.2 A. The inhibitors described in this work extend farther into the S' subsites of cathepsins than any inhibitors reported in the literature thus far. These interactions appear to make use of a S3' subsite that can potentially be exploited for enhanced specificity and/or affinity.

PubMed: 18278855
DOI: 10.1021/jm701190v

Experimental method

X-RAY DIFFRACTION (2.2 Å)