› 5frb

X-ray diffraction
2.99Å resolution

Crystal structure of sterol 14-alpha demethylase (CYP51B) from a pathogenic filamentous fungus Aspergillus fumigatus in complex with a tetrazole-based inhibitor VT-1598

Released:
DOI: 10.2210/pdb5frb/pdb
PDB entry 5frb coloured by chain, front view.
PDB entry 5frb coloured by chain, side view.
PDB entry 5frb coloured by chain, top view.
Source organism: Aspergillus fumigatus
Primary publication:
Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity.
Hargrove TY, Garvey EP, Hoekstra WJ, Yates CM, Wawrzak Z, Rachakonda G, Villalta F, Lepesheva GI
Antimicrob Agents Chemother 61 (2017)
PMID: 28461309

Function and Biology Details

Reaction catalysed: 
(1a) a 14-alpha-methylsteroid + [reduced NADPH--hemoprotein reductase] + O(2) = a 14-alpha-hydroxysteroid + [oxidized NADPH--hemoprotein reductase] + H(2)O
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-123228 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Sterol 14-alpha demethylase cyp51B Chain: A
Molecule details ›
Chain: A
Length: 473 amino acids
Theoretical weight: 53.58 KDa
Source organism: Aspergillus fumigatus
Expression system: Escherichia coli
UniProt:
  • Canonical: E9QY26 (Residues: 50-518; Coverage: 90%)
Gene names: AFUA_7G03740, cyp51B
Sequence domains: Cytochrome P450

Ligands and Environments

2 bound ligands:
Ligand HEM 1 x HEM
Ligand VT2 1 x VT2
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-F
Spacegroup: P3121
Unit cell:
a: 109.857Å b: 109.857Å c: 84.838Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.26 0.258 0.28
Expression system: Escherichia coli

Quick links

Citations

13 review citations

Antifungal resistance: current trends and future strategies to combat.
Wiederhold NP. (2017)
12 more

8 mentions without citation

The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors.
Zhang et al. (2019)
7 more