› 4zx8

X-ray diffraction
2.7Å resolution

X-ray crystal structure of PfA-M17 in complex with hydroxamic acid-based inhibitor 9b

Released:
DOI: 10.2210/pdb4zx8/pdb
PDB entry 4zx8 coloured by chain, front view.
PDB entry 4zx8 coloured by chain, side view.
PDB entry 4zx8 coloured by chain, top view.
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

Reaction catalysed: 
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:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo hexamer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-100131 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
leucyl aminopeptidase 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

7 bound ligands:
Ligand 4TY 12 x 4TY
Ligand ZN 24 x ZN
Ligand CO3 12 x CO3
Ligand GOL 6 x GOL
Ligand DMS 1 x DMS
Ligand 1PE 26 x 1PE
Ligand SO4 13 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: AUSTRALIAN SYNCHROTRON BEAMLINE MX2
Spacegroup: P212121
Unit cell:
a: 174.393Å b: 177.47Å c: 231.292Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.199 0.197 0.245
Expression system: Escherichia coli BL21

Quick links

Citations

5 review citations

M1 aminopeptidases as drug targets: broad applications or therapeutic niche?
Drinkwater et al. (2017)
4 more

2 mentions without citation

Novel Molecular Synapomorphies Demarcate Different Main Groups/Subgroups of Plasmodium and Piroplasmida Species Clarifying Their Evolutionary Relationships.
Sharma et al. (2019)
1 more