de Oliveira_2019_Int.J.Biol.Macromol_129_653

Reference

Title : The molecular structure of an epoxide hydrolase from Trichoderma reesei in complex with urea or amide-based inhibitors - de Oliveira_2019_Int.J.Biol.Macromol_129_653
Author(s) : de Oliveira GS , Adriani PP , Ribeiro JA , Morisseau C , Hammock BD , Dias MVB , Chambergo FS
Ref : Int J Biol Macromol , 129 :653 , 2019
Abstract :

Epoxide hydrolases (EHs) are enzymes involved in the metabolism of endogenous and exogenous epoxides, and the development of EH inhibitors has important applications in the medicine. In humans, EH inhibitors are being tested in the treatment of cardiovascular diseases and show potent anti-inflammatory effects. EH inhibitors are also considerate promising molecules against infectious diseases. EHs are functionally very well studied, but only a few members have its three-dimensional structures characterized. Recently, a new EH from the filamentous fungi Trichoderma reseei (TrEH) was reported, and a series of urea or amide-based inhibitors were identified. In this study, we describe the crystallographic structures of TrEH in complex with five different urea or amide-based inhibitors with resolutions ranging from 2.6 to 1.7A. The analysis of these structures reveals the molecular basis of the inhibition of these compounds. We could also observe that these inhibitors occupy the whole extension of the active site groove and only a few conformational changes are involved. Understanding the structural basis EH interactions with different inhibitors might substantially contribute for the study of fungal metabolism and in the development of novel and more efficient antifungal drugs against pathogenic Trichoderma species.

PubMedSearch : de Oliveira_2019_Int.J.Biol.Macromol_129_653
PubMedID: 30771398
Gene_locus related to this paper: hypjq-g0r7e2

Related information

Inhibitor 6N3Z-4    6N5G-2    6N3K-1    6N5F-3    t-AUCB
Gene_locus 6N3Z-4    6N5G-2    6N3K-1    6N5F-3    t-AUCB    hypjq-g0r7e2
Structure 6N3Z-4    6N5G-2    6N3K-1    6N5F-3    t-AUCB    hypjq-g0r7e2    6N3K    6N3Z    6N5F    6N5H    6N5G

Citations formats

de Oliveira GS, Adriani PP, Ribeiro JA, Morisseau C, Hammock BD, Dias MVB, Chambergo FS (2019)
The molecular structure of an epoxide hydrolase from Trichoderma reesei in complex with urea or amide-based inhibitors
Int J Biol Macromol 129 :653

de Oliveira GS, Adriani PP, Ribeiro JA, Morisseau C, Hammock BD, Dias MVB, Chambergo FS (2019)
Int J Biol Macromol 129 :653