Download MendeleyStructural and Functional Perturbation of Giardia Lamblia Triosephosphate Isomerase by Modification of a Non-Catalytic, Non-Conserved Region.
Hernandez-Alcantara, G., Torres-Larios, A., Enriquez-Flores, S., Garcia-Torres, I., Castillo-Villanueva, A., Mendez, S.T., De La Mora-De La Mora, I., Gomez-Manzo, S., Torres-Arroyo, A., Lopez-Velazquez, G., Reyes-Vivas, H., Oria-Hernandez, J.(2013) PLoS One 8: 69031
- PubMed: 23894402
- DOI: https://doi.org/10.1371/journal.pone.0069031
- Primary Citation of Related Structures:
4BI5, 4BI6, 4BI7 - PubMed Abstract:
We have previously proposed triosephosphate isomerase of Giardia lamblia (GlTIM) as a target for rational drug design against giardiasis, one of the most common parasitic infections in humans. Since the enzyme exists in the parasite and the host, selective inhibition is a major challenge because essential regions that could be considered molecular targets are highly conserved. Previous biochemical evidence showed that chemical modification of the non-conserved non-catalytic cysteine 222 (C222) inactivates specifically GlTIM. The inactivation correlates with the physicochemical properties of the modifying agent: addition of a non-polar, small chemical group at C222 reduces the enzyme activity by one half, whereas negatively charged, large chemical groups cause full inactivation.
Organizational Affiliation:
Laboratorio de Bioquímica-Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, Mexico.
