Structural highlights
Function
[CYSP_TRYCR] Hydrolyzes chromogenic peptides at the carboxyl Arg or Lys; requires at least one more amino acid, preferably Arg, Phe, Val or Leu, between the terminal Arg or Lys and the amino-blocking group. The cysteine protease may play an important role in the development and differentiation of the parasites at several stages of their life cycle.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
We describe here the identification of non-peptidic vinylsulfones that inhibit parasite cysteine proteases in vitro and inhibit the growth of Trypanosoma brucei brucei parasites in culture. A high resolution (1.75 A) co-crystal structure of 8a bound to cruzain reveals how the non-peptidic P2/P3 moiety in such analogs bind the S2 and S3 subsites of the protease, effectively recapitulating important binding interactions present in more traditional peptide-based protease inhibitors and natural substrates.
Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases.,Bryant C, Kerr ID, Debnath M, Ang KK, Ratnam J, Ferreira RS, Jaishankar P, Zhao D, Arkin MR, McKerrow JH, Brinen LS, Renslo AR Bioorg Med Chem Lett. 2009 Nov 1;19(21):6218-21. Epub 2009 Sep 3. PMID:19773167[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bryant C, Kerr ID, Debnath M, Ang KK, Ratnam J, Ferreira RS, Jaishankar P, Zhao D, Arkin MR, McKerrow JH, Brinen LS, Renslo AR. Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6218-21. Epub 2009 Sep 3. PMID:19773167 doi:10.1016/j.bmcl.2009.08.098
