› 4x2t

X-ray diffraction
2.73Å resolution

X-ray crystal structure of the orally available aminopeptidase inhibitor, Tosedostat, bound to the M17 Leucyl Aminopeptidase from P. falciparum

Released:
DOI: 10.2210/pdb4x2t/pdb
PDB 4x2t coloured by chain and viewed from the front.
PDB 4x2t coloured by chain and viewed from the side.
PDB 4x2t coloured by chain and viewed from the top.
Source organism: Plasmodium falciparum 3D7
Primary publication:
X-ray crystal structures of an orally available aminopeptidase inhibitor, Tosedostat, bound to anti-malarial drug targets PfA-M1 and PfA-M17.
Drinkwater N, Bamert RS, Sivaraman KK, Paiardini A, McGowan S
Proteins (2015)
PMID: 25645579

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:
Leucine 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: 519 amino acids
Theoretical weight: 57.56 KDa
Source organism: Plasmodium falciparum 3D7
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: Q8IL11 (Residues: 85-603; Coverage: 86%)
Gene names: LAP, PF3D7_1446200
Sequence domains: Cytosol aminopeptidase family, catalytic domain
Structure domains:

Ligands and Environments

5 bound ligands:
Ligand ZN 24 x ZN
Ligand TOD 11 x TOD
Ligand CO3 12 x CO3
Ligand SO4 13 x SO4
Ligand 1PE 10 x 1PE
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: AUSTRALIAN SYNCHROTRON BEAMLINE MX2
Spacegroup: P212121
Unit cell:
a: 173.715Å b: 176.698Å c: 223.977Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.222 0.22 0.274
Expression system: Escherichia coli BL21

Quick links

Citations

5 citation in other articles

Excretion/secretion products from Schistosoma mansoni adults, eggs and schistosomula have unique peptidase specificity profiles.
Dvořák et al. (2016)
4 more