Table 1.
Target status of N. fowleri proteins within SSGCID pipeline.
Table 2.
Listing of Naegleria fowleri structures deposited by SSGCID in the PDB.
Table 3.
Comparative analysis of N. fowleri and human structures deposited the PDB.
Fig 1.
A. Quaternary structure of NfSAHH (5V96) with chain A, B, C and D colored blue, green, pink and yellow respectively with ligands ADO and NAD colored red and orange respectively. B. Structural alignment of Chain A HsSAHH (1LI4) and Chain A NfSAHH (5V96) colored pink and blue respectively with NAD ligand colored orange and neplanocin inhibitor colored red. C. Depiction of the electron density surrounding the NAD ligand from 5V96 model. |Fo|–|Fc| electron density omit map shown sculpted around NAD ligand at 2.0 Å, calculated using the composite-omit-map function of Phenix [25]. Residues which contact the ligand within 4 Å are shown in ball and stick (blue:nitrogen; red: oxygen; gray:carbon). Dotted lines represent polar contacts within 4 Å of the ligand, calculated using PyMol [26]. Conserved Lys and Tyr residues are directly labelled with Thr383 exhibiting the human amino acid substitution. D. Depiction of the electron density surrounding the oxadiazole compound from 5W49 model. |Fo|–|Fc| electron density omit map shown sculpted around the oxadiazole compound at 2.0 Å, calculated using the composite-omit-map function of Phenix [25]. Residues which contact the ligand within 4 Å are shown in ball and stick (blue:nitrogen; red: oxygen; gray:carbon). Dotted lines represent polar contacts within 4 Å of the ligand, calculated using PyMol [26]. Met351 coordinating the oxadiazole compound is also labelled. E. Structural alignment of Chain A HsSAHH, PDB ID: 1LI4 and Chain A NfSAHH, PDB ID: 5V96 with close-up to additional helix insertion of NfSAHH. Hydrophobic groove formed by Val163, Leu166, Val169 and Leu 173 at opening of adenosine pocket.
Fig 2.
A. Quaternary structure of NfPGM (5VVE) with chain A and B colored blue and green respectively with coordinated chloride ion in lime. B. Structural alignment of Chain A HsPGM (5Y65) and Chain A NfPGM (5V96) colored pink and blue respectively with KH2 inhibitor and 2-morpholin-4-ium-4-ylethanesulfonic acid colored red and yellow respectively. Divergent residues (Thr30; Nf and Ser30;Hs) within citrate acid binding pocket are shown in as sticks and annotated.
Fig 3.
A. Quaternary structure of NfPRMT1 (6CU5) with chain A and B colored blue and green respectively with SAH ligands in red. B. Structural alignment of Chain A HsPRMT1 (6NT2) and Chain A NfPRMT1 (6CU5) colored pink and blue respectively with SAH ligand and GSK3368715 colored yellow and red respectively. C. Depiction of the electron density surrounding the GSK3368715 inhibitor from the 6NT2 model. |Fo|–|Fc| electron density omit map shown sculpted around GSK3368715 inhibitor at 2.0 Å, calculated using the composite-omit-map function of Phenix [25]. N-terminal residues which contact the ligand within 4 Å are shown in ball and stick (blue:nitrogen; red: oxygen; gray:carbon) and are labelled. All labelled residues are within the allosteric inhibition site of HsPRMT1.
Fig 4.
A. Quaternary structure of NfPPI (6MKE) with chain A, B, C and D colored blue, green, pink and yellow respectively with FK506 ligands in red. B. Structural alignment of Chain A HsPPI (4DRO) and Chain A NfPGM (6MKE) colored pink and blue respectively with FK506-AN inhibitor and FKBP51 colored red and yellow respectively. C. Depiction of the electron density surrounding the FK506-AN inhibitor from the 6MKE model. |Fo|–|Fc| electron density omit map shown sculpted around FK506-AN inhibitor at 2.0 Å, calculated using the composite-omit-map function of Phenix [25]. Residues which contact the ligand within 4 Å are shown in ball and stick (blue:nitrogen; red: oxygen; gray:carbon). Dotted lines represent polar contacts within 4 Å of the ligand, calculated using PyMol [26]. Conserved polar interactions are labelled. D. Depiction of the electron density surrounding the FKBP51 compound from the 4DRO model. |Fo|–|Fc| electron density omit map shown sculpted around the FKBP51 compound at 2.0 Å, calculated using the composite-omit-map function of Phenix [25]. Surrounding in a gray cartoon is Chain A of the HsPPI with hydrophilic residues surrounding the active site that diverge from the NfPPI hydrophobic residues annotated.
Fig 5.
Structure of the NfProRS A. Quaternary structure of NfProRS (6UYH). Homodimeric structure depicted with individual polypeptide chains A and B colored blue and green respectively with AMP-PNP ligands, halofuginone inhibitors and sulfate ions in red, orange and yellow respectively. B. Structural alignment of Chain A HsProRS (5VAD) and Chain A NfPRMT (6NAB) colored pink and blue respectively with AMP-PNP and ADO ligands colored red and yellow respectively. C. The three structure-function domains of NfProRS (6NAB). The catalytic, anticodon binding, and editing domains are colored cyan, green, and orange; respectively. D. The three highly conserved sequence motifs that characterize class II ARSs. Motif 1, colored lime, comprises the dimer interface. Motif 2, colored red, forms part of the acceptor stem. Motif 3, colored blue, is involved in forming the activated prolyl-adenylate. E. Structural alignment of halofuginone bound NfProRS in tan with halofuginone colored orange (6UYH) and halofuginone absent NfProRS in blue (6NAB). Close up of disordered loop associated with halofuginone binding and phenylalanine positions in each loop configuration.