| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-176 |
Sentence |
denotes |
Structure-Functional Characterization of Cytochrome P450 Sterol 14α-Demethylase (CYP51B) from Aspergillus fumigatus and Molecular Basis for the Development of Antifungal Drugs. |
| T2 |
177-327 |
Sentence |
denotes |
Aspergillus fumigatus is the opportunistic fungal pathogen that predominantly affects the immunocompromised population and causes 600,000 deaths/year. |
| T3 |
328-515 |
Sentence |
denotes |
The cytochrome P450 51 (CYP51) inhibitor voriconazole is currently the drug of choice, yet the treatment efficiency remains low, calling for rational development of more efficient agents. |
| T4 |
516-614 |
Sentence |
denotes |
A. fumigatus has two CYP51 genes, CYP51A and CYP51B, which share 59% amino acid sequence identity. |
| T5 |
615-699 |
Sentence |
denotes |
CYP51B is expressed constitutively, whereas gene CYP51A is reported to be inducible. |
| T6 |
700-1039 |
Sentence |
denotes |
We expressed, purified, and characterized A. fumigatus CYP51B, including determination of its substrate preferences, catalytic parameters, inhibition, and x-ray structure in complexes with voriconazole and the experimental inhibitor (R)-N-(1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide (VNI). |
| T7 |
1040-1321 |
Sentence |
denotes |
The enzyme demethylated its natural substrate eburicol and the plant CYP51 substrate obtusifoliol at steady-state rates of 17 and 16 min(-1), respectively, but did not metabolize lanosterol, and the topical antifungal drug miconazole was the strongest inhibitor that we identified. |
| T8 |
1322-1543 |
Sentence |
denotes |
The x-ray crystal structures displayed high overall similarity of A. fumigatus CYP51B to CYP51 orthologs from other biological kingdoms but revealed phylum-specific differences relevant to enzyme catalysis and inhibition. |
| T9 |
1544-1834 |
Sentence |
denotes |
The complex with voriconazole provides an explanation for the potency of this relatively small molecule, whereas the complex with VNI outlines a direction for further enhancement of the efficiency of this new inhibitory scaffold to treat humans afflicted with filamentous fungal infections. |
