› 4zyq

X-ray diffraction
2.6Å resolution

X-ray crystal structure of PfA-M17 in complex with hydroxamic acid-based inhibitor 10s

Released:
DOI: 10.2210/pdb4zyq/pdb
PDB 4zyq coloured by chain and viewed from the front.
PDB 4zyq coloured by chain and viewed from the side.
PDB 4zyq coloured by chain and viewed from the top.
Source organism: Plasmodium falciparum FcB1/Columbia
Primary publication:
Potent dual inhibitors of Plasmodium falciparum M1 and M17 aminopeptidases through optimization of S1 pocket interactions.
Drinkwater N, Vinh NB, Mistry SN, Bamert RS, Ruggeri C, Holleran JP, Loganathan S, Paiardini A, Charman SA, Powell AK, Avery VM, McGowan S, Scammells PJ
Eur J Med Chem 110 43-64 (2016)
PMID: 26807544

Function and Biology Details

Reactions catalysed: 
Release of N-terminal proline from a peptide.
Release of an N-terminal amino acid, Xaa-|-Yaa-, in which Xaa is preferably Leu, but may be other amino acids including Pro although not Arg or Lys, and Yaa may be Pro. Amino acid amides and methyl esters are also readily hydrolyzed, but rates on arylamides are exceedingly low.
Biochemical function:
  • not assigned
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
homo hexamer (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Cytosol aminopeptidase domain-containing protein Chains: A, B, C, D, E, F, G, H, I, J, K, L
Molecule details ›
Chains: A, B, C, D, E, F, G, H, I, J, K, L
Length: 522 amino acids
Theoretical weight: 57.98 KDa
Source organism: Plasmodium falciparum FcB1/Columbia
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: A0A024V0B1 (Residues: 84-605; Coverage: 86%)
Gene name: PFFVO_05086
Sequence domains: Cytosol aminopeptidase family, catalytic domain
Structure domains:

Ligands and Environments

5 bound ligands:
Ligand 4U6 12 x 4U6
Ligand ZN 24 x ZN
Ligand CO3 12 x CO3
Ligand 1PE 20 x 1PE
Ligand SO4 8 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: AUSTRALIAN SYNCHROTRON BEAMLINE MX2
Spacegroup: P212121
Unit cell:
a: 174.436Å b: 176.565Å c: 230.997Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.194 0.192 0.244
Expression system: Escherichia coli BL21

Quick links

Citations

4 review citations

Driving antimalarial design through understanding of target mechanism.
Calic et al. (2020)
3 more