A three-dimensional structure of Plasmodium falciparum serine hydroxymethyltransferase in complex with glycine and 5-formyl-tetrahydrofolate. Homology modeling and molecular dynamics.
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.
França
Tanos C C
TC
Departamento de Química, Instituto Militar de Engenharia, Praça General Tibúrcio 80-Urca, Rio de Janeiro, Brazil.
Pascutti
Pedro G
PG
Ramalho
Teodorico C
TC
Figueroa-Villar
Jose D
JD
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
D012696:Glycine Hydroxymethyltransferase; D002955:Leucovorin; D005998:Glycine