Computational Identification of Uncharacterized Cruzain Binding Sites

• Published in: PLoS neglected tropical diseases Vol. 4; no. 5; p. e676
• Main Authors: Durrant, Jacob D., Keränen, Henrik, Wilson, Benjamin A., McCammon, J. Andrew
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2010; Public Library of Science (PLoS)
• Subjects: Antiprotozoal Agents - metabolism; Binding Sites; Biochemistry/Drug Discovery; Biochemistry/Theory and Simulation; Biologi; Biology; Computational Biology - methods; Computational Biology/Comparative Sequence Analysis; Computational Biology/Molecular Dynamics; Cysteine Endopeptidases - genetics; Infections; Infectious Diseases/Neglected Tropical Diseases; Infectious Diseases/Protozoal Infections; Medical research; MEDICIN; MEDICINE; Models, Molecular; NATURAL SCIENCES; NATURVETENSKAP; Parasites; Protease Inhibitors - metabolism; Protein Binding; Proteins; Protozoan Proteins - antagonists & inhibitors; Protozoan Proteins - genetics; Tropical diseases; Trypanosoma cruzi - enzymology; Vector-borne diseases; Cysteine Endopeptidases; Antiprotozoal Agents; Protease Inhibitors; Computational Biology; Models, Molecular; Protein Binding; Protozoan Proteins; Binding Sites; Trypanosoma cruzi
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0000676

Chagas disease, caused by the unicellular parasite Trypanosoma cruzi, claims 50,000 lives annually and is the leading cause of infectious myocarditis in the world. As current antichagastic therapies like nifurtimox and benznidazole are highly toxic, ineffective at parasite eradication, and subject to increasing resistance, novel therapeutics are urgently needed. Cruzain, the major cysteine protease of Trypanosoma cruzi, is one attractive drug target. In the current work, molecular dynamics simulations and a sequence alignment of a non-redundant, unbiased set of peptidase C1 family members are used to identify uncharacterized cruzain binding sites. The two sites identified may serve as targets for future pharmacological intervention.