› 5tz1

X-ray diffraction
2Å resolution

Crystal structure of sterol 14-alpha demethylase (CYP51) from Candida albicans in complex with the tetrazole-based antifungal drug candidate VT1161 (VT1)

Released:
DOI: 10.2210/pdb5tz1/pdb
PDB entry 5tz1 coloured by chain, front view.
PDB entry 5tz1 coloured by chain, side view.
PDB entry 5tz1 coloured by chain, top view.
Source organism: Candida albicans
Primary publication:
Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis.
Hargrove TY, Friggeri L, Wawrzak Z, Qi A, Hoekstra WJ, Schotzinger RJ, York JD, Guengerich FP, Lepesheva GI
J Biol Chem 292 6728-6743 (2017)
PMID: 28258218

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-145358 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Lanosterol 14-alpha demethylase Chains: A, B
Molecule details ›
Chains: A, B
Length: 490 amino acids
Theoretical weight: 56.44 KDa
Source organism: Candida albicans
Expression system: Escherichia coli K-12
UniProt:
  • Canonical: P10613 (Residues: 48-528; Coverage: 91%)
Gene names: CAALFM_C500660CA, CYP51, CaO19.922, ERG11, ERG16
Sequence domains: Cytochrome P450

Ligands and Environments

2 bound ligands:
Ligand HEM 2 x HEM
Ligand VT1 2 x VT1
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-F
Spacegroup: C2
Unit cell:
a: 177.64Å b: 71.44Å c: 79.19Å
α: 90° β: 96.63° γ: 90°
R-values:
R R work R free
0.218 0.218 0.224
Expression system: Escherichia coli K-12

Quick links

Citations

10 review citations

Formation and Cleavage of C-C Bonds by Enzymatic Oxidation-Reduction Reactions.
Guengerich et al. (2018)
9 more

42 mentions without citation

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