title: A three-dimensional structure of Plasmodium falciparum serine hydroxymethyltransferase in complex with glycine and 5-formyl-tetrahydrofolate. Homology modeling and molecular dynamics.
abstract: Cytosolic Plasmodium falciparum serine hydroxymethyltransferase (pfSHMT) is a potential target for antimalarial chemotherapy. Contrasting with the other enzymes involved in the parasite folate cycle, little information is available about this enzyme, and its crystallographic structure is unknown yet. In this paper, we propose a theoretical low-resolution 3D model for pfSHMT in complex with glycine and 5-formyl tetrahydrofolate (5-FTHF) based on homology modeling by multiple alignment followed by intensive optimization, validation and dynamics simulations in water. Comparison between the active sites of our model and that of crystallographic Human SHMT (hSHMT) revealed key differences that could be useful for the design of new selective inhibitors of pfSHMT.
authors.affiliation: Departamento de Química, Instituto Militar de Engenharia, Praça General Tibúrcio 80-Urca, Rio de Janeiro, Brazil.
authors.forename: Tanos C C
authors.initials: TC
authors.lastname: França
authors.forename: Pedro G
authors.initials: PG
authors.lastname: Pascutti
authors.forename: Teodorico C
authors.initials: TC
authors.lastname: Ramalho
authors.forename: Jose D
authors.initials: JD
authors.lastname: Figueroa-Villar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000201:enzymology; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D005998:Glycine / Q000737:chemistry*; D012696:Glycine Hydroxymethyltransferase / Q000737:chemistry*; D006801:Humans; D021621:Imaging, Three-Dimensional; D002955:Leucovorin / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000201:enzymology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D012696:Glycine Hydroxymethyltransferase; D002955:Leucovorin; D005998:Glycine