title: Structure of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase complexed with chalepin, a natural product inhibitor, at 1.95 A resolution.
abstract: The structure of the glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi complexed with chalepin, a natural product from Pilocarpus spicatus, has been determined by X-ray crystallography to 1.95 A resolution. The structure is in the apo form without cofactors in the subunits of the tetrameric gGAPDH in the asymmetric unit. Unequivocal density corresponding to the inhibitor was clearly identified in one monomer. The final refined model of the complex shows extensive conformational changes when compared with the native structure. The mode of binding of chalepin to gGAPDH and its implications for inhibitor design are discussed.
authors.affiliation: Instituto de Química de São Carlos, USP, São Carlos, SP, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Pavão
authors.forename: M S
authors.initials: MS
authors.lastname: Castilho
authors.forename: M T
authors.initials: MT
authors.lastname: Pupo
authors.forename: R L A
authors.initials: RL
authors.lastname: Dias
authors.forename: A G
authors.initials: AG
authors.lastname: Correa
authors.forename: J B
authors.initials: JB
authors.lastname: Fernandes
authors.forename: M F G F
authors.initials: MF
authors.lastname: da Silva
authors.forename: J
authors.initials: J
authors.lastname: Mafezoli
authors.forename: P C
authors.initials: PC
authors.lastname: Vieira
authors.forename: G
authors.initials: G
authors.lastname: Oliva
mesh_terms: D000818:Animals; D003460:Crystallization; D018360:Crystallography, X-Ray; D011564:Furocoumarins / Q000737:chemistry* / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D046911:Macromolecular Substances; D008830:Microbodies / Q000201:enzymology*; D015394:Molecular Structure; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000235:genetics
chemical_list: D011564:Furocoumarins; D046911:Macromolecular Substances; C031533:chalepin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases